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Title: A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion
Author: 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
Keywords: Fibroblasts
Patologia cel·lular
Cellular pathology
Issue Date: 1-Mar-2017
Publisher: Nature Publishing Group
Abstract: 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.
Note: Versió postprint del document publicat a:
It is part of: Nature Cell Biology, 2017, vol. 19, num. 3, p. 224-237
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ISSN: 1465-7392
Appears in Collections:Articles publicats en revistes (Biomedicina)

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