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E-cadherin loss is associated with increased cell invasion in gastric carcinoma, and germline mutations of the E-cadherin gene are causative of hereditary diffuse gastric cancer. Although E-cadherin dysfunction impacts cell\u2013cell adhesion, cell dissemination also requires an imbalance of adhesion to the extracellular matrix (ECM).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>To identify ECM components and receptors relevant for adhesion of E-cadherin dysfunctional cells, we implemented a novel ECM microarray platform coupled with molecular interaction networks. The functional role of putative candidates was determined by combining micropattern traction microscopy, protein modulation and in vivo approaches, as well as transcriptomic data of 262 gastric carcinoma samples, retrieved from the cancer genome atlas (TCGA).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Here, we show that E-cadherin mutations induce an abnormal interplay of cells with specific components of the ECM, which encompasses increased traction forces and Integrin \u03b21 activation. Integrin \u03b21 synergizes with E-cadherin dysfunction, promoting cell scattering and invasion. The significance of the E-cadherin-Integrin \u03b21 crosstalk was validated in <jats:italic>Drosophila<\/jats:italic> models and found to be consistent with evidence from human gastric carcinomas, where increased tumour grade and poor survival are associated with low E-cadherin and high Integrin \u03b21 levels.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Integrin \u03b21 is a key mediator of invasion in carcinomas with E-cadherin impairment and should be regarded as a biomarker of poor prognosis in gastric cancer.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10120-021-01239-9","type":"journal-article","created":{"date-parts":[[2021,9,5]],"date-time":"2021-09-05T19:02:21Z","timestamp":1630868541000},"page":"124-137","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Integrin \u03b21 orchestrates the abnormal cell-matrix attachment and invasive behaviour of E-cadherin dysfunctional cells"],"prefix":"10.1007","volume":"25","author":[{"given":"Joana","family":"Figueiredo","sequence":"first","affiliation":[]},{"given":"Rui M.","family":"Ferreira","sequence":"additional","affiliation":[]},{"given":"Han","family":"Xu","sequence":"additional","affiliation":[]},{"given":"Margarida","family":"Gon\u00e7alves","sequence":"additional","affiliation":[]},{"given":"Andr\u00e9","family":"Barros-Carvalho","sequence":"additional","affiliation":[]},{"given":"Janine","family":"Cravo","sequence":"additional","affiliation":[]},{"given":"Andr\u00e9 F.","family":"Maia","sequence":"additional","affiliation":[]},{"given":"Patr\u00edcia","family":"Carneiro","sequence":"additional","affiliation":[]},{"given":"C\u00e9u","family":"Figueiredo","sequence":"additional","affiliation":[]},{"given":"Michael L.","family":"Smith","sequence":"additional","affiliation":[]},{"given":"Dimitrije","family":"Stamenovi\u0107","sequence":"additional","affiliation":[]},{"given":"Eurico","family":"Morais-de-S\u00e1","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8851-4166","authenticated-orcid":false,"given":"Raquel","family":"Seruca","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2021,9,5]]},"reference":[{"key":"1239_CR1","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1038\/ncb3136","volume":"17","author":"T Lecuit","year":"2015","unstructured":"Lecuit T, Yap AS. 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