A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion
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Anna Labernadie Takuya Kato Agustí Brugués Xavier Serra-Picamal Stefanie Derzsi Esther Arwert Anne Weston Victor González-Tarragó Alberto Elosegui Artola Lorenzo Albertazzi Jordi Alcaraz Pere Roca-Cusachs Erik Sahai Xavier TrepatAbstract
Cancer-associated fibroblasts (CAFs) promote tumour invasion and metastasis. We show that CAFs exert a physical force on cancer cells that enables their collective invasion. Force transmission is mediated by a heterophilic adhesion involving N-cadherin at the CAF membrane and E-cadherin at the cancer cell membrane. This adhesion is mechanically active; when subjected to force it triggers β-catenin recruitment and adhesion reinforcement dependent on α-catenin/vinculin interaction. Impairment of E-cadherin/N-cadherin adhesion abrogates the ability of CAFs to guide collective cell migration and blocks cancer cell invasion. N-cadherin also mediates repolarization of the CAFs away from the cancer cells. In parallel, nectins and afadin are recruited to the cancer cell/CAF interface and CAF repolarization is afadin dependent. Heterotypic junctions between CAFs and cancer cells are observed in patient-derived material. Together, our findings show that a mechanically active heterophilic adhesion between CAFs and cancer cells enables cooperative tumour invasion.
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Journal Nature Cell Biology
Volume 19
Issue number 3
Pages 224-237
Available online
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Publisher website (DOI) 10.1038/ncb3478
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Europe PubMed Central 28218910
Pubmed 28218910
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