A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion

作者：Labernadie, Anna; Kato, Takuya; Brugues, Agusti; Serra-Picamal, Xavier; Derzsi, Stefanie; Arwert, Esther; Weston, Anne; Gonzalez-Tarrago, Victor; Elosegui-Artola, Alberto; Albertazzi, Lorenzo; Alcaraz, Jordi; Roca-Cusachs, Pere; Sahai, Erik^*; Trepat, Xavier^*

来源：Nature Cell Biology, 2017, 19(3): 224-237.

DOI：10.1038/ncb3478

• REGULATES CONTACT INHIBITION
• BREAST-CANCER
• MESENCHYMAL TRANSITION
• TUMOR MICROENVIRONMENT
• COLLECTIVE INVASION
• ADHERENS JUNCTIONS
• ALPHA-CATENIN
• MIGRATION
• FORCES
• LOCOMOTION

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 beta-catenin recruitment and adhesion reinforcement dependent on alpha-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.

• 出版日期2017-3