Title:
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A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion
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Author:
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Labernadie, Anna; Kato, Takuya; Brugués, Agustí; Serra Picamal, Xavier; Derzsi, Stefanie; Arwert, Esther; Weston, Anne; González Tarragó, Víctor; Elosegui-Artola, Alberto; Albertazzi, Lorenzo; Alcaraz Casademunt, Jordi; Roca-Cusachs Soulere, Pere; Sahai, Erik; Trepat Guixer, Xavier
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Other authors:
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Universitat de Barcelona |
Abstract:
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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. |
Subject(s):
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-Fibroblasts -Tumors -Patologia cel·lular -Fibroblasts -Tumors -Cellular pathology |
Rights:
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(c) Labernadie, Anna et al., 2017
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Document type:
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Article Article - Accepted version |
Published by:
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Nature Publishing Group
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