Publications

@article{romaniello_nf-kb_2025,

title = {NF-kB oscillation profiles decode response to anti-EGFR monoclonal antibodies},

author = {Donatella Romaniello and Lorenzo Dall'Olio and Martina Mazzeschi and Anna Francia and Federica Pagano and Valerio Gelfo and Gabriele D'Uva and Enrico Giampieri and Mattia Lauriola},

url = {https://linkinghub.elsevier.com/retrieve/pii/S2472555225000127},

doi = {10.1016/j.slasd.2025.100219},

issn = {24725552},

year  = {2025},

date = {2025-03-01},

urldate = {2025-06-10},

journal = {SLAS Discovery},

volume = {31},

pages = {100219},

abstract = {A direct connection between an inflammatory environment and cancer has been extensively proven over the years. We previously reported that the presence of interleukin 1 (IL-1) is responsible for the lack of response to monoclonal antibody targeting epidermal growth factor receptor (EGFR) in colorectal cancer (CRC). Considering the driver role of NF-kB in controlling the expression of IL-1, herein, we investigate the dynamics of the oscillatory profile of the NF-kB response to monoclonal antibody, on the background of an inflammatory environment. NF-kB is a typical transcription factor that displays intrinsic oscillatory behavior, whose biological relevance in term for example of decoding response to monoclonal antibodies, remains unclear. Using live cell luciferase techniques, we recorded NF-kB activity over time in response to cetuximab (CTX) alone or in combination with IL-1 cytokines. Our results revealed an additive effect of these two agents on NF-kB activation, which was specific to CTX responsive cells. In contrast, CTX resistant cells did not display a significant change in the NF-kB profile under the IL-1 plus CTX combination. These results suggest an immediate interactive crosstalk between IL-1 and EGFR in the activation of NF-kB signaling pathway, which may lay the basis for the development of drug tolerant persister cells (DTP), leading to CTX resistance.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{ferlizza_extracellular_2023,

title = {Extracellular Vesicles and Epidermal Growth Factor Receptor Activation: Interplay of Drivers in Cancer Progression},

author = {Enea Ferlizza and Donatella Romaniello and Francesco Borrelli and Federica Pagano and Cinzia Girone and Valerio Gelfo and Rikke Sofie Kuhre and Alessandra Morselli and Martina Mazzeschi and Michela Sgarzi and Daria Maria Filippini and Gabriele D’Uva and Mattia Lauriola},

url = {https://www.mdpi.com/2072-6694/15/11/2970},

doi = {10.3390/cancers15112970},

issn = {2072-6694},

year  = {2023},

date = {2023-05-01},

urldate = {2025-06-10},

journal = {Cancers},

volume = {15},

number = {11},

pages = {2970},

abstract = {Extracellular vesicles (EVs) are of great interest to study the cellular mechanisms of cancer development and to diagnose and monitor cancer progression. EVs are a highly heterogeneous population of cell derived particles, which include microvesicles (MVs) and exosomes (EXOs). EVs deliver intercellular messages transferring proteins, lipids, nucleic acids, and metabolites with implications for tumour progression, invasiveness, and metastasis. Epidermal Growth Factor Receptor (EGFR) is a major driver of cancer. Tumour cells with activated EGFR could produce EVs disseminating EGFR itself or its ligands. This review provides an overview of EVs (mainly EXOs and MVs) and their cargo, with a subsequent focus on their production and effects related to EGFR activation. In particular, in vitro studies performed in EGFR-dependent solid tumours and/or cell cultures will be explored, thus shedding light on the interplay between EGFR and EVs production in promoting cancer progression, metastases, and resistance to therapies. Finally, an overview of liquid biopsy approaches involving EGFR and EVs in the blood/plasma of EGFR-dependent tumour patients will also be discussed to evaluate their possible application as candidate biomarkers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{romaniello_senescence-associated_2022,

title = {Senescence-associated reprogramming induced by interleukin-1 impairs response to EGFR neutralization},

author = {Donatella Romaniello and Valerio Gelfo and Federica Pagano and Enea Ferlizza and Michela Sgarzi and Martina Mazzeschi and Alessandra Morselli and Carmen Miano and Gabriele D’Uva and Mattia Lauriola},

url = {https://cmbl.biomedcentral.com/articles/10.1186/s11658-022-00319-7},

doi = {10.1186/s11658-022-00319-7},

issn = {1425-8153, 1689-1392},

year  = {2022},

date = {2022-12-01},

urldate = {2025-06-10},

journal = {Cellular & Molecular Biology Letters},

volume = {27},

number = {1},

pages = {20},

abstract = {Abstract 

 Background 

 EGFR targeting is currently the main treatment strategy for metastatic colorectal cancer (mCRC). Results of different clinical trials show that patients with wild-type KRAS and BRAF benefit from anti-EGFR monoclonal antibodies (moAbs) cetuximab (CTX) or panitumumab. Unfortunately, despite initial response, patients soon became refractory. Tumor heterogeneity and multiple escaping routes have been addressed as the main culprit, and, behind genomic alterations already described, changes in signaling pathways induced by drug pressure are emerging as mechanisms of acquired resistance. We previously reported an association between reduced sensitivity to CTX and increased expression of IL-1. However, how IL-1 mediates CTX resistance in mCRC is still unclear. 

 Methods 

 Under CTX treatment, the upregulation of IL-1R1 expression and a senescence program in sensitive colorectal cancer (CRC) cell lines is examined over time using qPCR, immunoblotting, and immunofluorescence. 

 Results 

 In sensitive CRC cells, IL-1 appeared responsible for a CTX-mediated G0 phase arrest. On the contrary, CTX-resistant CRC cells (CXR) maintained high mRNA levels of IL-1R1 and a post-senescence reprogramming, as indicated by increased SNAIL expression. Interestingly, treatment of CXR cells with a recombinant decoy, able to sequester the soluble form of IL-1, pushed CTX-resistant CRC cells back into a stage of senescence, thus blocking their proliferation. Our model suggests a trans-regulatory mechanism mediated by IL-1 on EGFR signaling. By establishing senescence and regulating EGFR activity and expression, IL-1 exposure ultimately bestows resistance. 

 Conclusions 

 To sum up, our findings point to the combined blockage of IL-1R and EGFR as a promising therapeutical approach to restore sensitivity to EGFR-targeting monoclonal antibodies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{miano_nrg1erbb3erbb2_2022,

title = {NRG1/ERBB3/ERBB2 Axis Triggers Anchorage-Independent Growth of Basal-like/Triple-Negative Breast Cancer Cells},

author = {Carmen Miano and Alessandra Morselli and Francesca Pontis and Chiara Bongiovanni and Francesca Sacchi and Silvia Da Pra and Donatella Romaniello and Riccardo Tassinari and Michela Sgarzi and Elvira Pantano and Carlo Ventura and Mattia Lauriola and Gabriele D’Uva},

url = {https://www.mdpi.com/2072-6694/14/7/1603},

doi = {10.3390/cancers14071603},

issn = {2072-6694},

year  = {2022},

date = {2022-03-01},

urldate = {2025-06-10},

journal = {Cancers},

volume = {14},

number = {7},

pages = {1603},

abstract = {ERBB3, also known as HER3, is a tyrosine kinase transmembrane receptor of the ERBB family. Upon binding to neuregulin 1 (NRG1), ERBB3 preferentially dimerizes with HER2 (ERBB2), in turn inducing aggressive features in several cancer types. The analysis of a dataset of breast cancer patients unveiled that higher ERBB3 mRNA expression correlates with shorter relapse-free survival in basal-like breast cancers, despite low ERBB3 expression in this breast cancer subtype. Administration of neuregulin 1 beta (NRG1β) significantly affected neither cellular proliferation nor the basal migratory ability of basal-like/triple-negative quasi-normal MCF10A breast cells, cultured in mono-layer conditions. Furthermore, no significant regulation in cell morphology or in the expression of basal/myoepithelial and luminal markers was observed upon stimulation with NRG1β. In non-adherent conditions, NRG1β administration to MCF10A cells did not significantly influence cell survival; however, it robustly induced cell growth as spheroids (3D growth). Intriguingly, a remarkable upregulation of ERBB3 and ERBB2 protein abundance was observed in 3D compared to 2D cell cultures, and NRG1β-induced 3D cell growth was efficiently prevented by the anti-HER2 monoclonal antibody pertuzumab. Similar results were obtained by the analysis of basal-like/triple-negative breast cancer cellular models, MDA-MB-468 and MDA-MB-231 cells, in which NRG1β induced anchorage-independent cell growth that in turn was prevented or reduced by the simultaneous administration of anti-HER2 neutralizing antibodies. Finally, the ability of pertuzumab in suppressing NRG1β-induced 3D growth was also evaluated and confirmed in MCF10A engineered with HER2-overexpression. We suggest that the NRG1/ERBB3/ERBB2 pathway promotes the anchorage-independent growth of basal-like breast cancer cells. Importantly, we provide evidence that ERBB2 neutralization, in particular by pertuzumab, robustly inhibits this process. Our results pave the way towards the development of novel anticancer strategies for basal-like breast cancer patients based on the interception of the NRG1/ERBB3/ERBB2 signaling axis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{ferlizza_roadmap_2021,

title = {The Roadmap of Colorectal Cancer Screening},

author = {Enea Ferlizza and Rossella Solmi and Michela Sgarzi and Luigi Ricciardiello and Mattia Lauriola},

url = {https://www.mdpi.com/2072-6694/13/5/1101},

doi = {10.3390/cancers13051101},

issn = {2072-6694},

year  = {2021},

date = {2021-03-01},

urldate = {2025-06-10},

journal = {Cancers},

volume = {13},

number = {5},

pages = {1101},

abstract = {Colorectal cancer (CRC) is the third most common form of cancer in terms of incidence and the second in terms of mortality worldwide. CRC develops over several years, thus highlighting the importance of early diagnosis. National screening programs based on fecal occult blood tests and subsequent colonoscopy have reduced the incidence and mortality, however improvements are needed since the participation rate remains low and the tests present a high number of false positive results. This review provides an overview of the CRC screening globally and the state of the art in approaches aimed at improving accuracy and participation in CRC screening, also considering the need for gender and age differentiation. New fecal tests and biomarkers such as DNA methylation, mutation or integrity, proteins and microRNAs are explored, including recent investigations into fecal microbiota. Liquid biopsy approaches, involving novel biomarkers and panels, such as circulating mRNA, micro- and long-non-coding RNA, DNA, proteins and extracellular vesicles are discussed. The approaches reported are based on quantitative PCR methods that could be easily applied to routine screening, or arrays and sequencing assays that should be better exploited to describe and identify candidate biomarkers in blood samples.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{ferlizza_colorectal_2020,

title = {Colorectal cancer screening: Assessment of CEACAM6, LGALS4, TSPAN8 and COL1A2 as blood markers in faecal immunochemical test negative subjects},

author = {Enea Ferlizza and Rossella Solmi and Rossella Miglio and Elena Nardi and Gabriella Mattei and Michela Sgarzi and Mattia Lauriola},

url = {https://linkinghub.elsevier.com/retrieve/pii/S2090123220300424},

doi = {10.1016/j.jare.2020.03.001},

issn = {20901232},

year  = {2020},

date = {2020-07-01},

urldate = {2025-06-10},

journal = {Journal of Advanced Research},

volume = {24},

pages = {99–107},

abstract = {Prevention is essential to reduce Colorectal Cancer (CRC) mortality. We previously reported a panel of four genes: CEACAM6, LGALS4, TSPAN8, COL1A2 (CELTiC) able to discriminate patients with CRC. Here, we assessed the CELTiC panel by quantitative polymerase chain reaction, in the blood of 174 healthy subjects, who resulted negative to the faecal immunochemical test (FITN). Using non-parametric statistic and multinomial logistic models, the FITN were compared to previously analysed subjects: 36 false positive FIT (NFIT), who were negative at colonoscopy, 36 patients with low risk lesions (LR) and 92 patients with high risk lesions or CRC (HR/CRC). FITN showed a significantly lower expression of the four genes when compared to HR/CRC. Moreover, FITN showed a significantly lower expression of TSPAN8 and COL1A2 compared to NFIT and LR patients. The multinomial logistic model confirmed that TSPAN8 alone specifically discriminated FITN from NFIT, LR and HR/CRC, while LGALS4 was able to differentiate FITN from false positive FIT. Finally, ROC curves analysis of the comparisons between FITN and HR/CRC, LR or NFIT reported AUC greater than 0.87, with a sensitivity and specificity of 83% and 76%, respectively. The CELTiC panel was confirmed a useful tool to identify CRC patients and to discriminate false FIT positive subjects.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{roth_silac_2018,

title = {SILAC identifies LAD1 as a filamin-binding regulator of actin dynamics in response to EGF and a marker of aggressive breast tumors},

author = {Lee Roth and Swati Srivastava and Moshit Lindzen and Aldema Sas-Chen and Michal Sheffer and Mattia Lauriola and Yehoshua Enuka and Ashish Noronha and Maicol Mancini and Sara Lavi and Gabi Tarcic and Gur Pines and Nava Nevo and Ori Heyman and Tamar Ziv and Oscar M. Rueda and Davide Gnocchi and Eli Pikarsky and Arie Admon and Carlos Caldas and Yosef Yarden},

url = {https://www.science.org/doi/10.1126/scisignal.aan0949},

doi = {10.1126/scisignal.aan0949},

issn = {1945-0877, 1937-9145},

year  = {2018},

date = {2018-01-01},

urldate = {2025-06-10},

journal = {Science Signaling},

volume = {11},

number = {515},

pages = {eaan0949},

abstract = {LAD1 coordinates EGF-stimulated changes in the cytoskeleton to support aggressive phenotypes in breast cancers. 

 , 

 LAD1 marks aggressive breast cancer 

 The actin cytoskeleton is a framework of filaments that gives cells shape. Dynamic regulation of the cytoskeleton coordinates complex cell behaviors, such as cell-cell communication, migration and invasion, and cell division, the regulation of which is critical to development, tissue homeostasis, and disease. Roth 

 et al. 

 showed that signaling by the epidermal growth factor receptor (EGFR) promoted cell migration–associated actin dynamics through the phosphorylation of the protein LAD-1 (see also the Focus by Chiasson-MacKenzie and McClatchey). LAD1 was also a marker of aggressive subtypes or cases of breast tumors in patient samples; thus, it might be a useful biomarker to inform clinical decisions. 

 , 

 Mutations mimicking growth factor–induced proliferation and motility characterize aggressive subtypes of mammary tumors. To unravel currently unknown players in these processes, we performed phosphoproteomic analysis on untransformed mammary epithelial cells (MCF10A) that were stimulated in culture with epidermal growth factor (EGF). We identified ladinin-1 (LAD1), a largely uncharacterized protein to date, as a phosphorylation-regulated mediator of the EGF-to-ERK pathway. Further experiments revealed that LAD1 mediated the proliferation and migration of mammary cells. LAD1 was transcriptionally induced, phosphorylated, and partly colocalized with actin stress fibers in response to EGF. Yeast two-hybrid, proximity ligation, and coimmunoprecipitation assays revealed that LAD1 bound to actin–cross-linking proteins called filamins. Cosedimentation analyses indicated that LAD1 played a role in actin dynamics, probably in collaboration with the scaffold protein 14-3-3σ (also called SFN). Depletion of LAD1 decreased the expression of transcripts associated with cell survival and inhibited the growth of mammary xenografts in an animal model. Furthermore, LAD1 predicts poor patient prognosis and is highly expressed in aggressive subtypes of breast cancer characterized as integrative clusters 5 and 10, which partly correspond to triple-negative and HER2-positive tumors. Thus, these findings reveal a cytoskeletal component that is critically involved in cell migration and the acquisition of oncogenic attributes in human mammary tumors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{li_adenomatous_2016,

title = {Adenomatous polyposis coli (APC) regulates miR17-92 cluster through β-catenin pathway in colorectal cancer},

author = {Y Li and M Lauriola and D Kim and M Francesconi and G D’Uva and D Shibata and M P Malafa and T J Yeatman and D Coppola and R Solmi and J Q Cheng},

url = {https://www.nature.com/articles/onc2015522},

doi = {10.1038/onc.2015.522},

issn = {0950-9232, 1476-5594},

year  = {2016},

date = {2016-09-01},

urldate = {2025-06-10},

journal = {Oncogene},

volume = {35},

number = {35},

pages = {4558–4568},

abstract = {Adenomatous polyposis coli (APC) mutation is the most common genetic change in sporadic colorectal cancer (CRC). Although deregulations of miRNAs have been frequently reported in this malignancy, APC-regulated miRNAs have not been extensively documented. Here, by using an APC-inducible cell line and array analysis, we identified a total of 26 deregulated miRNAs. Among them, members of miR-17-92 cluster were dramatically inhibited by APC and induced by enforced expression of β-catenin. Furthermore, we demonstrate that activated β-catenin resulted from APC loss binds to and activates the miR-17-92 promoter. Notably, enforced expression of miR-19a overrides APC tumor suppressor activity, and knockdown of miR-19a in cancer cells with compromised APC function reduced their aggressive features in vitro. Finally, we observed that expression of miR-19a significantly correlates with β-catenin levels in colorectal cancer specimens, and it is associated to the aggressive stage of tumor progression. Thus, our study reveals that miR-17-92 cluster is directly regulated by APC/β-catenin pathway and could be a potential therapeutic target in colon cancers with aberrant APC/β-catenin signaling.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{rodia_systematic_2016,

title = {Systematic large-scale meta-analysis identifies a panel of two mRNAs as blood biomarkers for colorectal cancer detection},

author = {Maria Teresa Rodia and Giampaolo Ugolini and Gabriella Mattei and Isacco Montroni and Davide Zattoni and Federico Ghignone and Giacomo Veronese and Giorgia Marisi and Mattia Lauriola and Pierluigi Strippoli and Rossella Solmi},

url = {https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.8108},

doi = {10.18632/oncotarget.8108},

issn = {1949-2553},

year  = {2016},

date = {2016-05-01},

urldate = {2025-06-10},

journal = {Oncotarget},

volume = {7},

number = {21},

pages = {30295–30306},

abstract = {Colorectal cancer (CRC) is the third most common cancer in the world. A significant survival rate is achieved if it is detected at an early stage. A whole blood screening test, without any attempt to isolate blood fractions, could be an important tool to improve early detection of colorectal cancer. We searched for candidate markers with a novel approach based on the Transcriptome Mapper (TRAM), aimed at identifying specific RNAs with the highest differential expression ratio between colorectal cancer tissue and normal blood samples. This tool permits a large-scale systematic meta-analysis of all available data obtained by microarray experiments. The targeting of RNA took into consideration that tumour phenotypic variation is associated with changes in the mRNA levels of genes regulating or affecting this variation. 

A real time quantitative reverse transcription polymerase chain reaction (qRT- PCR) was applied to the validation of candidate markers in the blood of 67 patients and 67 healthy controls. The expression of genes: TSPAN8, LGALS4, COL1A2 and CEACAM6 resulted as being statistically different. 

In particular ROC curves attested for TSPAN8 an AUC of 0.751 with a sensitivity of 83.6% and a specificity of 58.2% at a cut off of 10.85, while the panel of the two best genes showed an AUC of 0.861 and a sensitivity of 92.5% with a specificity of 67.2%. 

Our preliminary study on a total of 134 subjects showed promising results for a blood screening test to be validated in a larger cohort with the staging stratification and in patients with other gastrointestinal diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{duva_towards_2016,

title = {Towards the emerging crosstalk: ERBB family and steroid hormones},

author = {Gabriele D’Uva and Mattia Lauriola},

url = {https://linkinghub.elsevier.com/retrieve/pii/S1084952115002505},

doi = {10.1016/j.semcdb.2015.11.004},

issn = {10849521},

year  = {2016},

date = {2016-02-01},

urldate = {2025-06-10},

journal = {Seminars in Cell & Developmental Biology},

volume = {50},

pages = {143–152},

abstract = {Growth factors acting through receptor tyrosine kinases (RTKs) of ERBB family, along with steroid hormones (SH) acting through nuclear receptors (NRs), are critical signalling mediators of cellular processes. Deregulations of ERBB and steroid hormone receptors are responsible for several diseases, including cancer, thus demonstrating the central role played by both systems. 

This review will summarize and shed light on an emerging crosstalk between these two important receptor families. How this mutual crosstalk is attained, such as through extensive genomic and non-genomic interactions, will be addressed. In light of recent studies, we will describe how steroid hormones are able to fine-tune ERBB feedback loops, thus impacting on cellular output and providing a new key for understanding the complexity of biological processes in physiological or pathological conditions. 

In our understanding, the interactions between steroid hormones and RTKs deserve further attention. A system biology approach and advanced technologies for the analysis of RTK-SH crosstalk could lead to major advancements in molecular medicine, providing the basis for new routes of pharmacological intervention in several diseases, including cancer.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{enuka_circular_2016,

title = {Circular RNAs are long-lived and display only minimal early alterations in response to a growth factor},

author = {Yehoshua Enuka and Mattia Lauriola and Morris E. Feldman and Aldema Sas-Chen and Igor Ulitsky and Yosef Yarden},

url = {https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkv1367},

doi = {10.1093/nar/gkv1367},

issn = {0305-1048, 1362-4962},

year  = {2016},

date = {2016-02-01},

urldate = {2025-06-10},

journal = {Nucleic Acids Research},

volume = {44},

number = {3},

pages = {1370–1383},

abstract = {Circular RNAs (circRNAs) are widespread circles of non-coding RNAs with largely unknown function. Because stimulation of mammary cells with the epidermal growth factor (EGF) leads to dynamic changes in the abundance of coding and non-coding RNA molecules, and culminates in the acquisition of a robust migratory phenotype, this cellular model might disclose functions of circRNAs. Here we show that circRNAs of EGF-stimulated mammary cells are stably expressed, while mRNAs and microRNAs change within minutes. In general, the circRNAs we detected are relatively long-lived and weakly expressed. Interestingly, they are almost ubiquitously co-expressed with the corresponding linear transcripts, and the respective, shared promoter regions are more active compared to genes producing linear isoforms with no detectable circRNAs. These findings imply that altered abundance of circRNAs, unlike changes in the levels of other RNAs, might not play critical roles in signaling cascades and downstream transcriptional networks that rapidly commit cells to specific outcomes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{carvalho_antibody_2016,

title = {An antibody to amphiregulin, an abundant growth factor in patients’ fluids, inhibits ovarian tumors},

author = {S Carvalho and M Lindzen and M Lauriola and N Shirazi and S Sinha and A Abdul-Hai and K Levanon and J Korach and I Barshack and Y Cohen and A Onn and G Mills and Y Yarden},

url = {https://www.nature.com/articles/onc201593},

doi = {10.1038/onc.2015.93},

issn = {0950-9232, 1476-5594},

year  = {2016},

date = {2016-01-01},

urldate = {2025-06-10},

journal = {Oncogene},

volume = {35},

number = {4},

pages = {438–447},

abstract = {Growth factors of the epidermal growth factor (EGF)/neuregulin family are involved in tumor progression and, accordingly, antibodies that intercept a cognate receptor, epidermal growth factor receptor (EGFR)/ERBB1, or a co-receptor, HER2, have been approved for cancer therapy. Although they might improve safety and delay onset of chemoresistance, no anti-ligand antibodies have been clinically approved. To identify suitable ligands, we surveyed fluids from ovarian and lung cancer patients and found that amphiregulin (AREG) is the most abundant and generalized ligand secreted by advanced tumors. AREG is a low affinity EGFR ligand, which is upregulated following treatment with chemotherapeutic drugs. Because AREG depletion retarded growth of xenografted ovarian tumors in mice, we generated a neutralizing monoclonal anti-AREG antibody. The antibody inhibited growth of ovarian cancer xenografts and strongly enhanced chemotherapy efficacy. Taken together, these results raise the possibility that AREG and other low- or high-affinity binders of EGFR might serve as potential targets for cancer therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{duva_erbb2_2015,

title = {ERBB2 triggers mammalian heart regeneration by promoting cardiomyocyte dedifferentiation and proliferation},

author = {Gabriele D’Uva and Alla Aharonov and Mattia Lauriola and David Kain and Yfat Yahalom-Ronen and Silvia Carvalho and Karen Weisinger and Elad Bassat and Dana Rajchman and Oren Yifa and Marina Lysenko and Tal Konfino and Julius Hegesh and Ori Brenner and Michal Neeman and Yosef Yarden and Jonathan Leor and Rachel Sarig and Richard P. Harvey and Eldad Tzahor},

url = {https://www.nature.com/articles/ncb3149},

doi = {10.1038/ncb3149},

issn = {1465-7392, 1476-4679},

year  = {2015},

date = {2015-05-01},

urldate = {2025-06-10},

journal = {Nature Cell Biology},

volume = {17},

number = {5},

pages = {627–638},

abstract = {The murine neonatal heart can regenerate after injury through cardiomyocyte (CM) proliferation, although this capacity markedly diminishes after the first week of life. Neuregulin-1 (NRG1) administration has been proposed as a strategy to promote cardiac regeneration. Here, using loss- and gain-of-function genetic tools, we explore the role of the NRG1 co-receptor ERBB2 in cardiac regeneration. NRG1-induced CM proliferation diminished one week after birth owing to a reduction in ERBB2 expression. CM-specific Erbb2 knockout revealed that ERBB2 is required for CM proliferation at embryonic/neonatal stages. Induction of a constitutively active ERBB2 (caERBB2) in neonatal, juvenile and adult CMs resulted in cardiomegaly, characterized by extensive CM hypertrophy, dedifferentiation and proliferation, differentially mediated by ERK, AKT and GSK3β/β-catenin signalling pathways. Transient induction of caERBB2 following myocardial infarction triggered CM dedifferentiation and proliferation followed by redifferentiation and regeneration. Thus, ERBB2 is both necessary for CM proliferation and sufficient to reactivate postnatal CM proliferative and regenerative potentials.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{kedmi_egf_2015,

title = {EGF induces microRNAs that target suppressors of cell migration: miR-15b targets textitMTSS1 in breast cancer},

author = {Merav Kedmi and Nir Ben-Chetrit and Cindy Körner and Maicol Mancini and Noa Bossel Ben-Moshe and Mattia Lauriola and Sara Lavi and Francesca Biagioni and Silvia Carvalho and Hadas Cohen-Dvashi and Fernando Schmitt and Stefan Wiemann and Giovanni Blandino and Yosef Yarden},

url = {https://www.science.org/doi/10.1126/scisignal.2005866},

doi = {10.1126/scisignal.2005866},

issn = {1945-0877, 1937-9145},

year  = {2015},

date = {2015-03-01},

urldate = {2025-06-10},

journal = {Science Signaling},

volume = {8},

number = {368},

abstract = {Growth factor–induced metastasis involves microRNA-mediated repression of a tumor suppressor. 

 , 

 Micromanaging growth factor–induced metastasis 

 Epidermal growth factor (EGF) stimulates cell proliferation and tumor growth in part by triggering kinase-dependent changes in gene expression. Noncoding RNAs, such as microRNAs (miRNAs), reduce gene expression by binding to protein-encoding transcripts. Kedmi 

 et al 

 . found that EGF stimulated migration in mammary epithelial cells and also increased the abundance of a set of miRNAs. Of these, miR-15b promoted EGF-induced migration and reduced the abundance of metastasis suppressor protein 1 (MTSS1). The expression of 

 miR-15b 

 was higher in aggressive tumors than in adjacent normal tissue and inversely correlated with that of 

 MTSS1 

 . Knockdown of MTSS1 promoted the migratory behavior and the formation of migration-associated structures in cultured cells. Low abundance of MTSS1 correlated with shorter survival in patients, and low expression of 

 MTSS1 

 correlated with high expression of 

 miR-15b 

 in aggressive basal breast cancer tissue, suggesting that this pathway is important in breast cancer and could be targeted to reduce metastatic disease in patients. 

 , 

 Growth factors promote tumor growth and metastasis. We found that epidermal growth factor (EGF) induced a set of 22 microRNAs (miRNAs) before promoting the migration of mammary cells. These miRNAs were more abundant in human breast tumors relative to the surrounding tissue, and their abundance varied among breast cancer subtypes. One of these miRNAs, miR-15b, targeted the 3′ untranslated region of 

 MTSS1 

 ( 

 metastasis suppressor protein 1 

 ). Although xenografts in which MTSS1 was knocked down grew more slowly in mice initially, longer-term growth was unaffected. Knocking down MTSS1 increased migration and Matrigel invasion of nontransformed mammary epithelial cells. Overexpressing MTSS1 in an invasive cell line decreased cell migration and invasiveness, decreased the formation of invadopodia and actin stress fibers, and increased the formation of cellular junctions. In tissues from breast cancer patients with the aggressive basal subtype, an inverse correlation occurred with the high expression of 

 miRNA-15b 

 and the low expression of 

 MTSS1 

 . Furthermore, low abundance of MTSS1 correlated with poor patient prognosis. Thus, growth factor–inducible miRNAs mediate mechanisms underlying the progression of cancer.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{cohendvashi_navigator3_2015,

title = {Navigator‐3, a modulator of cell migration, may act as a suppressor of breast cancer progression},

author = {Hadas Cohen‐Dvashi and Nir Ben‐Chetrit and Roslin Russell and Silvia Carvalho and Mattia Lauriola and Sophia Nisani and Maicol Mancini and Nishanth Nataraj and Merav Kedmi and Lee Roth and Wolfgang Köstler and Amit Zeisel and Assif Yitzhaky and Jacques Zylberg and Gabi Tarcic and Raya Eilam and Yoav Wigelman and Rainer Will and Sara Lavi and Ziv Porat and Stefan Wiemann and Sara Ricardo and Fernando Schmitt and Carlos Caldas and Yosef Yarden},

url = {https://www.embopress.org/doi/10.15252/emmm.201404134},

doi = {10.15252/emmm.201404134},

issn = {1757-4676, 1757-4684},

year  = {2015},

date = {2015-03-01},

urldate = {2025-06-10},

journal = {EMBO Molecular Medicine},

volume = {7},

number = {3},

pages = {299–314},

abstract = {Abstract 

 Dissemination of primary tumor cells depends on migratory and invasive attributes. Here, we identify 

 Navigator‐3 

 ( 

 NAV 

 3 

 ), a gene frequently mutated or deleted in human tumors, as a regulator of epithelial migration and invasion. Following induction by growth factors, 

 NAV 

 3 localizes to the plus ends of microtubules and enhances their polarized growth. Accordingly, 

 NAV 

 3 

 depletion trimmed microtubule growth, prolonged growth factor signaling, prevented apoptosis and enhanced random cell migration. Mathematical modeling suggested that 

 NAV 

 3‐depleted cells acquire an advantage in terms of the way they explore their environment. In animal models, silencing 

 NAV 

 3 

 increased metastasis, whereas ectopic expression of the wild‐type form, unlike expression of two, relatively unstable oncogenic mutants from human tumors, inhibited metastasis. Congruently, analyses of > 2,500 breast and lung cancer patients associated low 

 NAV 

 3 

 with shorter survival. We propose that 

 NAV 

 3 inhibits breast cancer progression by regulating microtubule dynamics, biasing directionally persistent rather than random migration, and inhibiting locomotion of initiated cells. 

 , 

 Synopsis 

 image 

 A new potential suppressor of metastasis, Navigator‐3, acts by modulating migration patterns and conferring a lower probability to locate tissue escape routes. 

 Navigator‐3 ( 

 NAV 

 3), a nerve‐navigating gene of worms and a gene frequently mutated or deleted in human tumors, was identified herein as a potential suppressor of metastasis, which associates with good prognosis of breast cancer patients. 

 The 

 NAV 

 3 protein localizes to the growing end of microtubules, enhances their growth and augments the ability of cells to adhere to a migration course, while also slowing down migration rates. 

 Animal studies indicate that these cellular actions of 

 NAV 

 3 overall reduce the capacity of tumor cells to form metastases, and mathematical modeling attributes this to lower probability to locate rare or transient targets, such as escape routes within tissues. 

 NAV 

 3 cancer mutations affect different protein domains; analysis of two point mutants uncovered a destabilization effect, suggesting loss of function in cancer.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{ben-chetrit_synaptojanin_2015,

title = {Synaptojanin 2 is a druggable mediator of metastasis and the gene is overexpressed and amplified in breast cancer},

author = {Nir Ben-Chetrit and David Chetrit and Roslin Russell and Cindy Körner and Maicol Mancini and Ali Abdul-Hai and Tomer Itkin and Silvia Carvalho and Hadas Cohen-Dvashi and Wolfgang J. Koestler and Kirti Shukla and Moshit Lindzen and Merav Kedmi and Mattia Lauriola and Ziv Shulman and Haim Barr and Dalia Seger and Daniela A. Ferraro and Fresia Pareja and Hava Gil-Henn and Tsvee Lapidot and Ronen Alon and Fernanda Milanezi and Marc Symons and Rotem Ben-Hamo and Sol Efroni and Fernando Schmitt and Stefan Wiemann and Carlos Caldas and Marcelo Ehrlich and Yosef Yarden},

url = {https://www.science.org/doi/10.1126/scisignal.2005537},

doi = {10.1126/scisignal.2005537},

issn = {1945-0877, 1937-9145},

year  = {2015},

date = {2015-01-01},

urldate = {2025-06-10},

journal = {Science Signaling},

volume = {8},

number = {360},

abstract = {Small-molecule inhibitors of the lipid phosphatase synaptojanin 2 may prevent breast cancer metastasis. 

 , 

 Blocking Receptor Recycling to Prevent Metastasis 

 Blocking cancer cell metastasis can prolong patient survival. Ben-Chetrit 

 et al 

 . found that many patients with aggressive breast cancer have tumors with increased expression of 

 SYNJ2 

 , which encodes the lipid phosphatase synaptojanin 2. In cultured breast cancer cells, epidermal growth factor (EGF) triggered the localization of SYNJ2 to lamellipodia and invadopodia, which are cellular protrusions associated with invasive behavior. Knocking down SYNJ2 inhibited recycling of the EGF receptor to the cell surface and decreased the invasive behavior of cultured breast cancer cells. Expressing a phosphatase-deficient mutant of SYNJ2 in xenografted breast cancer cells suppressed tumor growth and lung metastasis in mice. A chemical screen identified SYNJ2 inhibitors that reduced cell invasion through a 3D matrix, suggesting that targeting SYNJ2 may prevent metastasis in breast cancer patients. 

 , 

 Amplified 

 HER2 

 , which encodes a member of the epidermal growth factor receptor (EGFR) family, is a target of effective therapies against breast cancer. In search for similarly targetable genomic aberrations, we identified copy number gains in 

 SYNJ2 

 , which encodes the 5′-inositol lipid phosphatase synaptojanin 2, as well as overexpression in a small fraction of human breast tumors. Copy gain and overexpression correlated with shorter patient survival and a low abundance of the tumor suppressor microRNA miR-31. SYNJ2 promoted cell migration and invasion in culture and lung metastasis of breast tumor xenografts in mice. Knocking down SYNJ2 impaired the endocytic recycling of EGFR and the formation of cellular lamellipodia and invadopodia. Screening compound libraries identified SYNJ2-specific inhibitors that prevented cell migration but did not affect the related neural protein SYNJ1, suggesting that SYNJ2 is a potentially druggable target to block cancer cell migration.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lauriola_diurnal_2014,

title = {Diurnal suppression of EGFR signalling by glucocorticoids and implications for tumour progression and treatment},

author = {Mattia Lauriola and Yehoshua Enuka and Amit Zeisel and Gabriele D’Uva and Lee Roth and Michal Sharon-Sevilla and Moshit Lindzen and Kirti Sharma and Nava Nevo and Morris Feldman and Silvia Carvalho and Hadas Cohen-Dvashi and Merav Kedmi and Nir Ben-Chetrit and Alon Chen and Rossella Solmi and Stefan Wiemann and Fernando Schmitt and Eytan Domany and Yosef Yarden},

url = {https://www.nature.com/articles/ncomms6073},

doi = {10.1038/ncomms6073},

issn = {2041-1723},

year  = {2014},

date = {2014-10-01},

urldate = {2025-06-10},

journal = {Nature Communications},

volume = {5},

number = {1},

pages = {5073},

abstract = {Abstract 

 Signal transduction by receptor tyrosine kinases (RTKs) and nuclear receptors for steroid hormones is essential for body homeostasis, but the cross-talk between these receptor families is poorly understood. We observed that glucocorticoids inhibit signalling downstream of EGFR, an RTK. The underlying mechanism entails suppression of EGFR’s positive feedback loops and simultaneous triggering of negative feedback loops that normally restrain EGFR. Our studies in mice reveal that the regulation of EGFR’s feedback loops by glucocorticoids translates to circadian control of EGFR signalling: EGFR signals are suppressed by high glucocorticoids during the active phase (night-time in rodents), while EGFR signals are enhanced during the resting phase. Consistent with this pattern, treatment of animals bearing EGFR-driven tumours with a specific kinase inhibitor was more effective if administered during the resting phase of the day, when glucocorticoids are low. These findings support a circadian clock-based paradigm in cancer therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{penaaltamira_transcription_2014,

title = {The transcription factor <span style="font-variant:small-caps;">CCAAT</span> enhancer‐binding protein β protects rat cerebellar granule neurons from apoptosis through its transcription‐activating isoforms},

author = {Emiliano Peña‐Altamira and Elisabetta Polazzi and Edoardo Moretto and Mattia Lauriola and Barbara Monti},

url = {https://onlinelibrary.wiley.com/doi/10.1111/ejn.12407},

doi = {10.1111/ejn.12407},

issn = {0953-816X, 1460-9568},

year  = {2014},

date = {2014-01-01},

urldate = {2025-06-10},

journal = {European Journal of Neuroscience},

volume = {39},

number = {2},

pages = {176–185},

abstract = {Abstract 

 CCAAT 

 enhancer‐binding protein β is a transcription factor that is involved in many brain processes, although its role in neuronal survival/death remains unclear. By using primary cultures of rat cerebellar granule neurons, we have shown here that 

 CCAAT 

 enhancer‐binding protein β is present as all of its isoforms: the transcriptional activators liver activator proteins 1 and 2, and the transcriptional inhibitor liver inhibitory protein. We have also shown that liver activator protein 1 undergoes post‐translational modifications, such as phosphorylation and sumoylation. These isoforms have different subcellular localizations, liver activator protein 2 being found in the cytosolic fraction only, liver inhibitory protein in the nucleus only, and liver activator protein 1 in both fractions. Through neuronal apoptosis induction by shifting mature cerebellar granule neurons to low‐potassium medium, we have demonstrated that nuclear liver activator protein 1 expression decreases and its phosphorylation disappears, whereas liver inhibitory protein levels increase in the nuclear fraction, suggesting a pro‐survival role for liver activator protein transcriptional activation and a pro‐apoptotic role for liver inhibitory protein transcriptional inhibition. To confirm this, we transfected cerebellar granule neurons with plasmids expressing liver activator protein 1, liver activator protein 2, or liver inhibitory protein respectively, and observed that both liver activator proteins, which increase 

 CCAAT 

 ‐dependent transcription, but not liver inhibitory protein, counteracted apoptosis, thus demonstrating the pro‐survival role of liver activator proteins. These data significantly improve our current understanding of the role of 

 CCAAT 

 enhancer‐binding protein β in neuronal survival/apoptosis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{duva_beta-cateninhur_2013,

title = {Beta-Catenin/HuR Post-Transcriptional Machinery Governs Cancer Stem Cell Features in Response to Hypoxia},

author = {Gabriele D’Uva and Sara Bertoni and Mattia Lauriola and Sabrina De Carolis and Annalisa Pacilli and Laura D’Anello and Donatella Santini and Mario Taffurelli and Claudio Ceccarelli and Yosef Yarden and Lorenzo Montanaro and Massimiliano Bonafé and Gianluca Storci},

editor = {Rajeev Samant},

url = {https://dx.plos.org/10.1371/journal.pone.0080742},

doi = {10.1371/journal.pone.0080742},

issn = {1932-6203},

year  = {2013},

date = {2013-11-01},

urldate = {2025-06-10},

journal = {PLoS ONE},

volume = {8},

number = {11},

pages = {e80742},

abstract = {Hypoxia has been long-time acknowledged as major cancer-promoting microenvironment. In such an energy-restrictive condition, post-transcriptional mechanisms gain importance over the energy-expensive gene transcription machinery. Here we show that the onset of hypoxia-induced cancer stem cell features requires the beta-catenin-dependent post-transcriptional up-regulation of CA9 and SNAI2 gene expression. In response to hypoxia, beta-catenin moves from the plasma membrane to the cytoplasm where it binds and stabilizes SNAI2 and CA9 mRNAs, in cooperation with the mRNA stabilizing protein HuR. We also provide evidence that the post-transcriptional activity of cytoplasmic beta-catenin operates under normoxia in basal-like/triple-negative breast cancer cells, where the beta-catenin knockdown suppresses the stem cell phenotype in vitro and tumor growth in vivo. In such cells, we unravel the generalized involvement of the beta-catenin-driven machinery in the stabilization of EGF-induced mRNAs, including the cancer stem cell regulator IL6. Our study highlights the crucial role of post-transcriptional mechanisms in the maintenance/acquisition of cancer stem cell features and suggests that the hindrance of cytoplasmic beta-catenin function may represent an unprecedented strategy for targeting breast cancer stem/basal-like cells.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{zeisel_qcma_2013,

title = {qCMA: A Desktop Application for Quantitative Collective Cell Migration Analysis},

author = {Amit Zeisel and Assif Yitzhaky and Cindy Koerner and Mattia Lauriola and Hadas Cohen-Dvashi and Wolfgang J. Köstler and Yosef Yarden and Stefan Wiemann and Eytan Domany},

url = {https://linkinghub.elsevier.com/retrieve/pii/S2472555222074779},

doi = {10.1177/1087057112461940},

issn = {24725552},

year  = {2013},

date = {2013-03-01},

urldate = {2025-06-10},

journal = {SLAS Discovery},

volume = {18},

number = {3},

pages = {356–360},

abstract = {Collective migration is an important cellular trait, which is intensely studied by both basic and translational researchers. Investigation of the underlying mechanisms necessitates high-throughput assays and computational algorithms capable of generating reproducible quantitative measurements of cell migration. We present a desktop tool that can be used easily by any researcher, to quantify both fluorescent and phase-contrast images produced in the course of commonly used gap closure (“scratch,” “wound healing”) collective migration assays. The software has a simple graphical interface that allows the user to tune the relevant parameters and process large numbers of images (or movies). The output contains segmented images and the numerical values inferred from them, allowing easy quantitative analysis of the results.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pradeep_modeling_2012-1,

title = {Modeling invasive breast cancer: growth factors propel progression of HER2-positive premalignant lesions},

author = {C-R Pradeep and A Zeisel and W J Köstler and M Lauriola and J Jacob-Hirsch and B Haibe-Kains and N Amariglio and N Ben-Chetrit and A Emde and I Solomonov and G Neufeld and M Piccart and I Sagi and C Sotiriou and G Rechavi and E Domany and C Desmedt and Y Yarden},

url = {https://www.nature.com/articles/onc2011547},

doi = {10.1038/onc.2011.547},

issn = {0950-9232, 1476-5594},

year  = {2012},

date = {2012-08-01},

urldate = {2025-06-10},

journal = {Oncogene},

volume = {31},

number = {31},

pages = {3569–3583},

abstract = {The HER2/neu oncogene encodes a receptor-like tyrosine kinase whose overexpression in breast cancer predicts poor prognosis and resistance to conventional therapies. However, the mechanisms underlying aggressiveness of HER2 (human epidermal growth factor receptor 2)-overexpressing tumors remain incompletely understood. Because it assists epidermal growth factor (EGF) and neuregulin receptors, we overexpressed HER2 in MCF10A mammary cells and applied growth factors. HER2-overexpressing cells grown in extracellular matrix formed filled spheroids, which protruded outgrowths upon growth factor stimulation. Our transcriptome analyses imply a two-hit model for invasive growth: HER2-induced proliferation and evasion from anoikis generate filled structures, which are morphologically and transcriptionally analogous to preinvasive patients’ lesions. In the second hit, EGF escalates signaling and transcriptional responses leading to invasive growth. Consistent with clinical relevance, a gene expression signature based on the HER2/EGF-activated transcriptional program can predict poorer prognosis of a subgroup of HER2-overexpressing patients. In conclusion, the integration of a three-dimensional cellular model and clinical data attributes progression of HER2-overexpressing lesions to EGF-like growth factors acting in the context of the tumor's microenvironment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pradeep_modeling_2012,

title = {Modeling ductal carcinoma in situ: a HER2–Notch3 collaboration enables luminal filling},

author = {C-R Pradeep and W J Köstler and M Lauriola and R Z Granit and F Zhang and J Jacob-Hirsch and G Rechavi and H B Nair and B T Hennessy and A M Gonzalez-Angulo and R R Tekmal and I Ben-Porath and G B Mills and E Domany and Y Yarden},

url = {https://www.nature.com/articles/onc2011279},

doi = {10.1038/onc.2011.279},

issn = {0950-9232, 1476-5594},

year  = {2012},

date = {2012-02-01},

urldate = {2025-06-10},

journal = {Oncogene},

volume = {31},

number = {7},

pages = {907–917},

abstract = {A large fraction of ductal carcinoma in situ (DCIS), a non-invasive precursor lesion of invasive breast cancer, overexpresses the HER2/neu oncogene. The ducts of DCIS are abnormally filled with cells that evade apoptosis, but the underlying mechanisms remain incompletely understood. We overexpressed HER2 in mammary epithelial cells and observed growth factor-independent proliferation. When grown in extracellular matrix as three-dimensional spheroids, control cells developed a hollow lumen, but HER2-overexpressing cells populated the lumen by evading apoptosis. We demonstrate that HER2 overexpression in this cellular model of DCIS drives transcriptional upregulation of multiple components of the Notch survival pathway. Importantly, luminal filling required upregulation of a signaling pathway comprising Notch3, its cleaved intracellular domain and the transcriptional regulator HES1, resulting in elevated levels of c-MYC and cyclin D1. In line with HER2–Notch3 collaboration, drugs intercepting either arm reverted the DCIS-like phenotype. In addition, we report upregulation of Notch3 in hyperplastic lesions of HER2 transgenic animals, as well as an association between HER2 levels and expression levels of components of the Notch pathway in tumor specimens of breast cancer patients. Therefore, it is conceivable that the integration of the Notch and HER2 signaling pathways contributes to the pathophysiology of DCIS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{martinelli_role_2011,

title = {A role for epidermal growth factor receptor in idiopathic pulmonary fibrosis onset},

author = {Marcella Martinelli and Angela Maria Grazia Pacilli and Stefano Rivetti and Mattia Lauriola and Luca Fasano and Paolo Carbonara and Gabriella Mattei and Ilaria Valentini and Luca Scapoli and Rossella Solmi},

url = {http://link.springer.com/10.1007/s11033-010-0594-0},

doi = {10.1007/s11033-010-0594-0},

issn = {0301-4851, 1573-4978},

year  = {2011},

date = {2011-10-01},

urldate = {2025-06-10},

journal = {Molecular Biology Reports},

volume = {38},

number = {7},

pages = {4613–4617},

abstract = {In idiopathic pulmonary fibrosis (IPF) patients the presence of missense polymorphisms (SNP) in members of the epidermal growth factor receptor (EGFR) family or their genetic association could influence the binding affinity of natural ligands, modifying the expression and the behavior of the correlated genes. EGFR family members are particularly involved in the epithelial injury and fibrotic process in IPF. Genetic variations in HER family of receptors may alter the possible therapeutic efficacy of EGFR inhibitors. This study aimed to analyze the relationships between IPF and specific EGF receptor family functional polymorphisms. We tested the presence of common EGFR, HER2 and HER3 non-synonymous SNPs in the peripheral blood of 20 Italian IPF patients and their association with the disease. Our data indicated that the HER2 variant allele frequency was significantly lower in patients than in controls, with an odds ratio of 0.31 (95% CI 0.080, 0.98). Our finding suggests that HER2 variant could be a protective factor against IPF onset.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{martinelli_egfr_2011,

title = {The EGFR R521K polymorphism influences the risk to develop colorectal cancer},

author = {Marcella Martinelli and Giampaolo Ugolini and Luca Scapoli and Stefano Rivetti and Mattia Lauriola and Gabriella Mattei and Giancarlo Rosati and Isacco Montroni and Alessio Manaresi and Davide Zattoni and Mario Taffurelli and Rossella Solmi},

url = {https://journals.sagepub.com/doi/full/10.3233/DMA-2011-0826},

doi = {10.3233/DMA-2011-0826},

issn = {18758592, 15740153},

year  = {2011},

date = {2011-08-01},

urldate = {2025-06-10},

journal = {Cancer Biomarkers},

volume = {8},

number = {2},

pages = {61–65},

abstract = {Epidermal growth factor receptor (EGFR) family members (EGFR, HER2, HER3 and HER4) have been extensively investigated for its possible involvement in cancer development and progression. In colorectal cancer (CRC) EGFR family has been found frequently over-expressed, thus therapy targeting EGFR has been developed. Interestingly, it has been observed that genetic variants in these receptors may alter the therapeutic efficacy of EGFR inhibitors. Polymorphic variants in members of the EGFR family could influence different biologic activities, such as ligands affinity, dimerization efficiency, kinase activity, expression levels, with a consequent impact in signalling pathways and cell behaviour. This study aimed to verify whether single nucleotide polymorphisms (SNPs) of EGFR family members could represent susceptibility factors able to influence the risk to develop CRC. Peripheral blood of 70 Italian colon cancer patients and 72 healthy controls was used as a source of genomic DNA to investigate EGFR, HER2 and HER3 common non-synonymous SNPs. Genetic association tests were performed to verify a possible relationship with CRC. Evidence of genotype association was found for the R521K EGFR polymorphism under a dominant mode of inheritance (Mid-P=0.031). Genotypes with the variant allele of EGFR R521K SNP confer a risk reduction to develop CRC.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{zwang_two_2011,

title = {Two Phases of Mitogenic Signaling Unveil Roles for p53 and EGR1 in Elimination of Inconsistent Growth Signals},

author = {Yaara Zwang and Aldema Sas-Chen and Yotam Drier and Tal Shay and Roi Avraham and Mattia Lauriola and Efrat Shema and Efrat Lidor-Nili and Jasmine Jacob-Hirsch and Ninette Amariglio and Yiling Lu and Gordon B. Mills and Gideon Rechavi and Moshe Oren and Eytan Domany and Yosef Yarden},

url = {https://linkinghub.elsevier.com/retrieve/pii/S1097276511003236},

doi = {10.1016/j.molcel.2011.04.017},

issn = {10972765},

year  = {2011},

date = {2011-05-01},

urldate = {2025-06-10},

journal = {Molecular Cell},

volume = {42},

number = {4},

pages = {524–535},

abstract = {Normal cells require continuous exposure to growth factors in order to cross a restriction point and commit to cell-cycle progression. This can be replaced by two short, appropriately spaced pulses of growth factors, where the first pulse primes a process, which is completed by the second pulse, and enables restriction point crossing. Through integration of comprehensive proteomic and transcriptomic analyses of each pulse, we identified three processes that regulate restriction point crossing: (1) The first pulse induces essential metabolic enzymes and activates p53-dependent restraining processes. (2) The second pulse eliminates, via the PI3K/AKT pathway, the suppressive action of p53, as well as (3) sets an ERK-EGR1 threshold mechanism, which digitizes graded external signals into an all-or-none decision obligatory for S phase entry. Together, our findings uncover two gating mechanisms, which ensure that cells ignore fortuitous growth factors and undergo proliferation only in response to consistent mitogenic signals.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lauriola_il23r_2011,

title = {IL23R, NOD2/CARD15, ATG16L1 and PHOX2B polymorphisms in a group of patients with Crohn's disease and correlation with sub-phenotypes},

author = {Lauriola},

url = {http://www.spandidos-publications.com/ijmm/27/3/469},

doi = {10.3892/ijmm.2010.591},

issn = {1107-3756},

year  = {2011},

date = {2011-03-01},

urldate = {2025-06-10},

journal = {International Journal of Molecular Medicine},

volume = {27},

number = {3},

abstract = {Recent genomic research has identified interleukin-23 receptor (IL23R), nucleotide-binding oligomerization domain containing 2 caspase-activation recruitment domain 15 (NOD2/CARD15), autophagy related 16-like 1 (ATG16L1) and paired-like homeobox 2b (PHOX2B) as susceptibility loci for Crohn's Disease (CD). Our aim was to investigate these gene variants in a group of CD patients and to analyse the correlation to sub-phenotypes such as gender, smoking habits, disease behaviour at diagnosis, severity of disease and extra-intestinal manifestations. Nineteen patients with CD and 20 healthy controls were included in the study. The gene variants IL23R rs7517847 and rs11209026, NOD2/CARD15 rs2066845, PHOX2B rs16853571, ATG16L1 rs2241879 and rs2241880 were genotyped by PCR followed by sequencing. The frequency of the G risk allele of IL23R rs7517847 was found to be increased in patients with CD (42%) compared to that in control subjects (20%) [odds ratio (OR), 2.9; 95% confidence interval [CI], 1.06-7.9; P=0.03]. In addition, the homozygous condition GG was also associated with CD (OR, 8.70; 95% CI, 0.9-81.6; P=0.038). The analysis of correlation of genotype to sub-phenotypes showed an association of ATG16L1 rs2241879 with the lack of extra-intestinal manifestations (OR, 0.03; 95% CI, 0.002-0.45; P=0.006), and the patients defined as non-smokers displayed an increased frequency of the risk allele C (P=0.03). The present study confirms the association of the heterozygous and homozygous IL23R rs7517847 variant with CD and suggests an additive effect of smoking to the ATG16L1 rs2241879 C risk allele SNP, in the context of the multifactorial model established for the development of CD and a protective effect of the same allele against extra-intestinal manifestations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{solmi_identification_2010,

title = {Identification by a Digital Gene Expression Displayer (DGED) and test by RT-PCR analysis of new mRNA candidate markers for colorectal cancer in peripheral blood},

author = {Solmi},

url = {http://www.spandidos-publications.com/ijo/37/2/519},

doi = {10.3892/ijo_00000701},

issn = {10196439, 17912423},

year  = {2010},

date = {2010-06-01},

urldate = {2025-06-10},

journal = {International Journal of Oncology},

volume = {37},

number = {2},

abstract = {Evidence from the literature widely supports the efficacy of screening for colorectal cancer (CRC) in reducing mortality. A blood-based assay, potentially, represents a more accessible early detection tool for the identification of circulating tumour cells originating from a primary tumour site in the body. The present work aimed at identifying a set of specific mRNAs expressed in colon tissue but not in blood cells. These mRNAs may represent useful markers for early detection of circulating colon cancer cells by a simple, qualitative RT-PCR assay, following RNA extraction from peripheral blood samples. Using a data-mining tool called cDNA digital gene expression displayer (DGED), based on serial analysis of gene expression (SAGE) from the Cancer Genome Anatomy Project (CGAP) database, 4-colon and 14-blood cDNA libraries were analyzed. We selected 7 genes expressed in colon tissue but not in blood and were able to test 6 of them by RT-PCR in peripheral blood of CRC patients and healthy controls. We present a relatively easy and highly reproducible technique for the detection of mRNA expression of genes as candidate markers of malignancy in blood samples of patients with colon cancer. SAGE DGED provided a list of the best candidate mRNAs predicted to detect colon cells in the blood, namely those encoding the following proteins: hypothetical protein LOC644844 (LOC644844, whose cDNA was not amplifiable), fatty acid binding protein 1 (FABP1), carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), mucin 13 cell surface associated (MUC13), guanylate cyclase activator 2A (GUCA2A), amiloride binding protein 1 (ABP1), galactoside-binding, solute carrier family 26, member 3 (SLC26A3). The mRNA expression of these genes was evaluated in 8 samples from subjects diagnosed with CRC and 9 from healthy controls. We observed the expression of 2 of the 6 investigated genes in the blood samples of the vast majority of patients considered, but also in a subset of the controls. Our data confirm the extreme sensitivity of RT-PCR, making this technique able to detect minimal amounts of mRNA expressed in a non-tissue-specific manner. Moreover, DGED remains a powerful tool to identify candidate epithelial markers in blood, such as colon related mRNAs. However, to date, none of these qualified as tumour markers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{solmi_displayed_2008,

title = {Displayed correlation between gene expression profiles and submicroscopic alterations in response to cetuximab, gefitinib and EGF in human colon cancer cell lines},

author = {Rossella Solmi and Mattia Lauriola and Mirko Francesconi and Désirée Martini and Manuela Voltattorni and Claudio Ceccarelli and Giampaolo Ugolini and Giancarlo Rosati and Simone Zanotti and Isacco Montroni and Gabriella Mattei and Mario Taffurelli and Donatella Santini and Furio Pezzetti and Alessandro Ruggeri and Gastone Castellani and Lia Guidotti and Domenico Coppola and Pierluigi Strippoli},

url = {http://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-8-227},

doi = {10.1186/1471-2407-8-227},

issn = {1471-2407},

year  = {2008},

date = {2008-12-01},

urldate = {2025-06-10},

journal = {BMC Cancer},

volume = {8},

number = {1},

pages = {227},

abstract = {Background 

EGFR is frequently overexpressed in colon cancer. We characterized HT-29 and Caco-2, human colon cancer cell lines, untreated and treated with cetuximab or gefitinib alone and in combination with EGF. 

Methods 

Cell growth was determined using a variation on the MTT assay. Cell-cycle analysis was conducted by flow cytometry. Immunohistochemistry was performed to evaluate EGFR expression and scanning electron microscopy (SEM) evidenced the ultrastructural morphology. Gene expression profiling was performed using hybridization of the microarray Ocimum Pan Human 40 K array A. 

Results 

Caco-2 and HT-29 were respectively 66.25 and 59.24 % in G0/G1. They maintained this level of cell cycle distribution after treatment, suggesting a predominantly differentiated state. Treatment of Caco-2 with EGF or the two EGFR inhibitors produced a significant reduction in their viability. SEM clearly showed morphological cellular transformations in the direction of cellular death in both cell lines treated with EGFR inhibitors. HT-29 and Caco-2 displayed an important reduction of the microvilli (which also lose their erect position in Caco-2), possibly invalidating microvilli absorption function. HT-29 treated with cetuximab lost their boundary contacts and showed filipodi; when treated with gefitinib, they showed some vesicles: generally membrane reshaping is evident. Both cell lines showed a similar behavior in terms of on/off switched genes upon treatment with cetuximab. The gefitinib global gene expression pattern was different for the 2 cell lines; gefitinib treatment induced more changes, but directly correlated with EGF treatment. 

In cetuximab or gefitinib plus EGF treatments there was possible summation of the morphological effects: cells seemed more weakly affected by the transformation towards apoptosis. The genes appeared to be less stimulated than for single drug cases. 

Conclusion 

This is the first study to have systematically investigated the effect of cetuximab or gefitinib, alone and in combination with EGF, on human colon cancer cell lines. The EGFR inhibitors have a weaker effect in the presence of EGF that binds EGFR. Cetuximab treatment showed an expression pattern that inversely correlates with EGF treatment. We found interesting cyto-morphological features closely relating to gene expression profile. Both drugs have an effect on differentiation towards cellular death.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{solmi_microarray-based_2006,

title = {Microarray-based identification and RT-PCR test screening for epithelial-specific mRNAs in peripheral blood of patients with colon cancer},

author = {Rossella Solmi and Giampaolo Ugolini and Giancarlo Rosati and Simone Zanotti and Mattia Lauriola and Isacco Montroni and Marco Del Governatore and Antonello Caira and Mario Taffurelli and Donatella Santini and Domenico Coppola and Lia Guidotti and Paolo Carinci and Pierluigi Strippoli},

url = {https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-6-250},

doi = {10.1186/1471-2407-6-250},

issn = {1471-2407},

year  = {2006},

date = {2006-12-01},

urldate = {2025-06-10},

journal = {BMC Cancer},

volume = {6},

number = {1},

pages = {250},

abstract = {Background 

The efficacy of screening for colorectal cancer using a simple blood-based assay for the detection of tumor cells disseminated in the circulation at an early stage of the disease is gaining positive feedback from several lines of research. This method seems able to reduce colorectal cancer mortality and may replace colonoscopy as the most effective means of detecting colonic lesions. 

Methods 

In this work, we present a new microarray-based high-throughput screening method to identifying candidate marker mRNAs for the early detection of epithelial cells diluted in peripheral blood cells. This method includes 1. direct comparison of different samples of colonic mucosa and of blood cells to identify consistent epithelial-specific mRNAs from among 20,000 cDNA assayed by microarray slides; 2. identification of candidate marker mRNAs by data analysis, which allowed selection of only 10 putative differentially expressed genes; 3. Selection of some of the most suitable mRNAs (TMEM69, RANBP3 and PRSS22) that were assayed in blood samples from normal subjects and patients with colon cancer as possible markers for the presence of epithelial cells in the blood, using reverse transcription – polymerase chain reaction (RT-PCR). 

Results 

Our present results seem to provide an indication, for the first time obtained by genome-scale screening, that a suitable and consistent colon epithelium mRNA marker may be difficult to identify. 

Conclusion 

The design of new approaches to identify such markers is warranted.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}