Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/120671
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 Tumors Patologia cel·lular Fibroblasts Tumors 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: https://doi.org/10.1038/ncb3478 |
It is part of: | Nature Cell Biology, 2017, vol. 19, num. 3, p. 224-237 |
URI: | http://hdl.handle.net/2445/120671 |
Related resource: | https://doi.org/10.1038/ncb3478 |
ISSN: | 1465-7392 |
Appears in Collections: | Articles publicats en revistes (Biomedicina) Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC)) |
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