Biophysical Society Thematic Meeting | Singapore

Mechanobiology of Disease

Friday Speaker Abstracts

A Mechanically Active Heterotypic Adhesion Enables Fibroblasts to Drive Cancer Cell Invasion Anna Labernadie 1 , Takuya Kato 2 , Agusti Brugues 1 , Xavier Serra-Picamal 1 , Stefanie Derzsi 1 , Victor Gonzalez-Tarrago 1 , Alberto Elosegui-Artola 1 , Jordi Alcaraz 4 , Pere Roca-Cusachs 1,4 , Erik Sahai 2 , Xavier Trepat 1,3,5 . 1 Institute for Bioengineering of Catalonia, Barcelona, Spain, 2 The Francis Crick Institute, London, United Kingdom, 4 University of Barcelona, Barcelona, Spain, 5 Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina, Barcelona, Spain. 3 Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain, Cancer Associated Fibroblasts (CAFs) promote tumor invasion and metastasis. Here 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. Impairment of E- cadherin/N-cadherin adhesion abrogates the ability of CAFs to guide collective cell migration in 2D and blocks cancer cell invasion in 3D. Further, N-cadherin mediates not only adhesion and invasion but also repolarization of the CAFs away from the cancer cells. E-cadherin/N-cadherin junctions between CAFs and cancer cells are observed in cells derived from human epidermal carcinoma and human non-small lung cell carcinoma. Together, our findings show that a mechanically active heterophilic adhesion between CAFs and cancer cells enables cooperative tumor invasion.

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