{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:55:25Z","timestamp":1772254525128,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T00:00:00Z","timestamp":1630108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/MED-GEN\/30356\/2017"],"award-info":[{"award-number":["PTDC\/MED-GEN\/30356\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/BTM-SAL\/30383\/2017"],"award-info":[{"award-number":["PTDC\/BTM-SAL\/30383\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/BIM-ONC\/0281\/2014"],"award-info":[{"award-number":["PTDC\/BIM-ONC\/0281\/2014"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["NORTE-01-0145-FEDER-000029"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000029"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/108009\/2015-SM"],"award-info":[{"award-number":["SFRH\/BD\/108009\/2015-SM"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/130708\/2017-MG"],"award-info":[{"award-number":["SFRH\/BD\/130708\/2017-MG"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["CEECIND\/00622\/2017"],"award-info":[{"award-number":["CEECIND\/00622\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>E-cadherin, encoded by CDH1, is an essential molecule for epithelial homeostasis, whose loss or aberrant expression results in disturbed cell\u2013cell adhesion, increased cell invasion and metastasis. Carriers of CDH1 germline mutations have a high risk of developing diffuse gastric cancer and lobular breast cancer, associated with the cancer syndrome Hereditary Diffuse Gastric Cancer (HDGC). The ubiquitous availability of cancer panels has led to the identification of an increasing amount of \u201cincidental\u201d CDH1 genetic variants that pose a serious clinical challenge. This has sparked intensive research aiming at an accurate classification of the variants and consequent validation of their clinical relevance. The present study addressed the significance of a novel CDH1 variant, G212E, identified in an unusually large pedigree displaying strong aggregation of diffuse gastric cancer. We undertook a comprehensive pipeline encompassing family data, in silico predictions, in vitro assays and in vivo strategies, which validated the deleterious phenotype induced by this genetic alteration. In particular, we demonstrated that the G212E variant affects the stability and localization, as well as the adhesive and anti-invasive functions of E-cadherin, triggering epithelial disruption and disorganization. Our findings illustrate the clinical implication of a complementary approach for effective variant categorization and patient management.<\/jats:p>","DOI":"10.3390\/cancers13174359","type":"journal-article","created":{"date-parts":[[2021,8,29]],"date-time":"2021-08-29T21:45:16Z","timestamp":1630273516000},"page":"4359","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Germline CDH1 G212E Missense Variant: Combining Clinical, In Vitro and In Vivo Strategies to Unravel Disease Burden"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1590-1974","authenticated-orcid":false,"given":"Joana","family":"Figueiredo","sequence":"first","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"}]},{"given":"F\u00e1tima","family":"Mercadillo","sequence":"additional","affiliation":[{"name":"Familial Cancer Clinical Unit, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0278-0827","authenticated-orcid":false,"given":"Soraia","family":"Melo","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"}]},{"given":"Alicia","family":"Barroso","sequence":"additional","affiliation":[{"name":"Familial Cancer Clinical Unit, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain"}]},{"given":"Margarida","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute for Molecular and Cell Biology (IBMC), University of Porto, 4200-135 Porto, Portugal"},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas de Abel Salazar (ICBAS), Universidade do Porto, 4050-313 Porto, Portugal"}]},{"given":"Jos\u00e9","family":"D\u00edaz-Tasende","sequence":"additional","affiliation":[{"name":"Endoscopy Unit, Gastroenterology Department, 12 de Octubre Universitary Hospital, 28041 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4404-9343","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Carneiro","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"}]},{"given":"Luis","family":"Robles","sequence":"additional","affiliation":[{"name":"Familial Cancer Unit, Medical Oncology Service, 12 de Octubre Universitary Hospital, 28041 Madrid, Spain"}]},{"given":"Francisco","family":"Colina","sequence":"additional","affiliation":[{"name":"Pathology Department, 12 de Octubre Universitary Hospital, 28041 Madrid, Spain"}]},{"given":"Carolina","family":"Ibarrola","sequence":"additional","affiliation":[{"name":"Pathology Department, 12 de Octubre Universitary Hospital, 28041 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5522-8844","authenticated-orcid":false,"given":"Jos\u00e9","family":"Perea","sequence":"additional","affiliation":[{"name":"Surgery Department, Fundaci\u00f3n Jim\u00e9nez D\u00edaz University Hospital, 28040 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3525-8231","authenticated-orcid":false,"given":"Eurico","family":"Morais-de-S\u00e1","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute for Molecular and Cell Biology (IBMC), University of Porto, 4200-135 Porto, Portugal"}]},{"given":"Raquel","family":"Seruca","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"},{"name":"Medical Faculty, University of Porto, 4200-319 Porto, Portugal"}]},{"given":"Miguel","family":"Urioste","sequence":"additional","affiliation":[{"name":"Familial Cancer Clinical Unit, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.ajhg.2021.03.010","article-title":"Machine learning-based reclassification of germline variants of unknown significance: The RENOVO algorithm","volume":"108","author":"Favalli","year":"2021","journal-title":"Am. J. Hum. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/s41586-018-0461-z","article-title":"Accurate classification of BRCA1 variants with saturation genome editing","volume":"562","author":"Findlay","year":"2018","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e000094","DOI":"10.1136\/esmoopen-2016-000094","article-title":"Integrating next-generation sequencing into clinical oncology: Strategies, promises and pitfalls","volume":"1","author":"Horak","year":"2016","journal-title":"ESMO Open"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/nrg3118","article-title":"Rare and common variants: Twenty arguments","volume":"13","author":"Gibson","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3904","DOI":"10.1091\/mbc.E15-03-0153","article-title":"The role of functional data in interpreting the effects of genetic variation","volume":"26","author":"Young","year":"2015","journal-title":"Mol. Biol. Cell"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Corso, G., Montagna, G., Figueiredo, J., La Vecchia, C., Fumagalli Romario, U., Fernandes, M.S., Seixas, S., Roviello, F., Trovato, C., and Guerini-Rocco, E. (2020). Hereditary Gastric and Breast Cancer Syndromes Related to CDH1 Germline Mutation: A Multidisciplinary Clinical Review. Cancers, 12.","DOI":"10.3390\/cancers12061598"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/32918","article-title":"E-cadherin germline mutations in familial gastric cancer","volume":"392","author":"Guilford","year":"1998","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e60","DOI":"10.1016\/S1470-2045(14)71016-2","article-title":"Familial gastric cancer: Genetic susceptibility, pathology, and implications for management","volume":"16","author":"Oliveira","year":"2015","journal-title":"Lancet. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1001\/jamaoncol.2014.168","article-title":"Hereditary Diffuse Gastric Cancer Syndrome: CDH1 Mutations and Beyond","volume":"1","author":"Hansford","year":"2015","journal-title":"JAMA Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e386","DOI":"10.1016\/S1470-2045(20)30219-9","article-title":"Hereditary diffuse gastric cancer: Updated clinical practice guidelines","volume":"21","author":"Blair","year":"2020","journal-title":"Lancet. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1136\/jmedgenet-2018-105807","article-title":"Clinical spectrum and pleiotropic nature of CDH1 germline mutations","volume":"56","author":"Figueiredo","year":"2019","journal-title":"J. Med. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1111\/his.13715","article-title":"Pathological features of total gastrectomy specimens from asymptomatic hereditary diffuse gastric cancer patients and implications for clinical management","volume":"73","author":"Rocha","year":"2018","journal-title":"Histopathology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1016\/j.gie.2018.02.008","article-title":"Phenotypic heterogeneity of hereditary diffuse gastric cancer: Report of a family with early-onset disease","volume":"87","author":"Gullo","year":"2018","journal-title":"Gastrointest. Endosc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1002\/path.2415","article-title":"Histopathological and molecular analysis of gastrectomy specimens from hereditary diffuse gastric cancer patients has implications for endoscopic surveillance of individuals at risk","volume":"216","author":"Barber","year":"2008","journal-title":"J. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1093\/hmg\/ddg048","article-title":"Identification of CDH1 germline missense mutations associated with functional inactivation of the E-cadherin protein in young gastric cancer probands","volume":"12","author":"Suriano","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1007\/s00109-006-0091-z","article-title":"A model to infer the pathogenic significance of CDH1 germline missense variants","volume":"84","author":"Suriano","year":"2006","journal-title":"J. Mol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1093\/hmg\/ddl093","article-title":"E-cadherin missense mutations, associated with hereditary diffuse gastric cancer (HDGC) syndrome, display distinct invasive behaviors and genetic interactions with the Wnt and Notch pathways in Drosophila epithelia","volume":"15","author":"Pereira","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Simoes-Correia, J., Figueiredo, J., Lopes, R., Stricher, F., Oliveira, C., Serrano, L., and Seruca, R. (2012). E-cadherin destabilization accounts for the pathogenicity of missense mutations in hereditary diffuse gastric cancer. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0033783"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/ejhg.2012.159","article-title":"The importance of E-cadherin binding partners to evaluate the pathogenicity of E-cadherin missense mutations associated to HDGC","volume":"21","author":"Figueiredo","year":"2013","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1038\/ejhg.2014.240","article-title":"Quantification of mutant E-cadherin using bioimaging analysis of in situ fluorescence microscopy. A new approach to CDH1 missense variants","volume":"23","author":"Sanches","year":"2015","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"25101","DOI":"10.1038\/srep25101","article-title":"Quantification of topological features in cell meshes to explore E-cadherin dysfunction","volume":"6","author":"Mestre","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1002\/humu.23650","article-title":"Specifications of the ACMG\/AMP variant curation guidelines for the analysis of germline CDH1 sequence variants","volume":"39","author":"Lee","year":"2018","journal-title":"Hum. Mutat."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Melo, S., Figueiredo, J., Fernandes, M.S., Goncalves, M., Morais-de-Sa, E., Sanches, J.M., and Seruca, R. (2017). Predicting the Functional Impact of CDH1 Missense Mutations in Hereditary Diffuse Gastric Cancer. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122687"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1038\/nprot.2009.86","article-title":"Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm","volume":"4","author":"Kumar","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat. Methods"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1093\/bioinformatics\/btr254","article-title":"A graphical interface for the FoldX forcefield","volume":"27","author":"Delgado","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"976","DOI":"10.2144\/00295bm09","article-title":"Site-directed mutagenesis of large (13-kb) plasmids in a single-PCR procedure","volume":"29","author":"Wang","year":"2000","journal-title":"Biotechniques"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"10266","DOI":"10.1038\/s41598-018-28570-z","article-title":"Geometric compensation applied to image analysis of cell populations with morphological variability: A new role for a classical concept","volume":"8","author":"Figueiredo","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_31","unstructured":"Okabe, A., Boots, B., Sugihara, K., Chiu, S.N., and Kendall, D.G. (2000). Definitions and Basic Properties of Voronoi Diagrams, in Spatial Tessellations: Concepts and Applications of Voronoi Diagrams, John Wiley & Sons."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/978-1-59745-583-1_10","article-title":"Recombinases and their use in gene activation, gene inactivation, and transgenesis","volume":"420","author":"Bischof","year":"2008","journal-title":"Methods Mol. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1007\/s10555-014-9528-y","article-title":"E-cadherin germline mutation carriers: Clinical management and genetic implications","volume":"33","author":"Corso","year":"2014","journal-title":"Cancer Metastasis Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/978-94-007-6570-2_7","article-title":"Germline missense mutants in hereditary diffuse gastric cancer","volume":"7","author":"Figueiredo","year":"2013","journal-title":"Spotlight Fam. Hered. Gastric Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/B978-0-12-394311-8.00015-7","article-title":"E-cadherin alterations in hereditary disorders with emphasis on hereditary diffuse gastric cancer","volume":"116","author":"Oliveira","year":"2013","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3566","DOI":"10.1093\/hmg\/ddn249","article-title":"Endoplasmic reticulum quality control: A new mechanism of E-cadherin regulation and its implication in cancer","volume":"17","author":"Figueiredo","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Corso, G., Corso, F., Bellerba, F., Carneiro, P., Seixas, S., Cioffi, A., La Vecchia, C., Magnoni, F., Bonanni, B., and Veronesi, P. (2021). Geographical Distribution of E-cadherin Germline Mutations in the Context of Diffuse Gastric Cancer: A Systematic Review. Cancers, 13.","DOI":"10.3390\/cancers13061269"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1016\/j.yexcr.2009.02.020","article-title":"E-cadherin mutations and cell motility: A genotype-phenotype correlation","volume":"315","author":"Mateus","year":"2009","journal-title":"Exp. Cell Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1136\/jmedgenet-2018-105361","article-title":"Associations of CDH1 germline variant location and cancer phenotype in families with hereditary diffuse gastric cancer (HDGC)","volume":"56","author":"Lo","year":"2019","journal-title":"J. Med. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1136\/jmg.2007.051268","article-title":"Germline E-cadherin mutations in familial lobular breast cancer","volume":"44","author":"Masciari","year":"2007","journal-title":"J. Med. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1136\/jmedgenet-2018-105337","article-title":"Hereditary lobular breast cancer with an emphasis on E-cadherin genetic defect","volume":"55","author":"Corso","year":"2018","journal-title":"J. Med. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1093\/hmg\/dds497","article-title":"Identification of germline mutations in the cancer predisposing gene CDH1 in patients with orofacial clefts","volume":"22","author":"Vogelaar","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1038\/gim.2017.11","article-title":"Blepharocheilodontic syndrome is a CDH1 pathway-related disorder due to mutations in CDH1 and CTNND1","volume":"19","author":"Ghoumid","year":"2017","journal-title":"Genet. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1136\/gut.47.2.262","article-title":"The E-cadherin gene (CDH1) variants T340A and L599V in gastric and colorectal cancer patients in Korea","volume":"47","author":"Kim","year":"2000","journal-title":"Gut"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1093\/hmg\/8.4.607","article-title":"Germline E-cadherin gene (CDH1) mutations predispose to familial gastric cancer and colorectal cancer","volume":"8","author":"Richards","year":"1999","journal-title":"Hum. Mol. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.semcancer.2005.05.004","article-title":"Matrigel: Basement membrane matrix with biological activity","volume":"15","author":"Kleinman","year":"2005","journal-title":"Semin. Cancer Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6188","DOI":"10.1021\/bi00267a025","article-title":"Isolation and characterization of type IV procollagen, laminin, and heparan sulfate proteoglycan from the EHS sarcoma","volume":"21","author":"Kleinman","year":"1982","journal-title":"Biochemistry"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1083\/jcb.200506131","article-title":"Regulatory mechanisms required for DE-cadherin function in cell migration and other types of adhesion","volume":"170","author":"Pacquelet","year":"2005","journal-title":"J. Cell Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.semcdb.2014.03.031","article-title":"Genetics and mechanisms of ovarian cancer: Parallels between Drosophila and humans","volume":"28","year":"2014","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.ceb.2019.07.016","article-title":"Polarity proteins in oncogenesis","volume":"62","author":"Fomicheva","year":"2020","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1111\/j.1349-7006.2009.01163.x","article-title":"Hereditary diffuse gastric cancer: A manifestation of lost cell polarity","volume":"100","author":"Humar","year":"2009","journal-title":"Cancer Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"13996","DOI":"10.1038\/ncomms13996","article-title":"Cell division orientation is coupled to cell-cell adhesion by the E-cadherin\/LGN complex","volume":"8","author":"Gloerich","year":"2017","journal-title":"Nat. Commun."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/17\/4359\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:54:24Z","timestamp":1760165664000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/17\/4359"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,28]]},"references-count":52,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["cancers13174359"],"URL":"https:\/\/doi.org\/10.3390\/cancers13174359","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,28]]}}}