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A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion
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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.
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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. A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion. _Nature Cell Biology_. 2017. Vol. 19, núm. 3, pàgs. 224-237. [consulta: 12 de febrer de 2026]. ISSN: 1465-7392. [Disponible a: https://hdl.handle.net/2445/120671]