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

By Anna Labernadie, Takuya Kato, A. Brugues, Xavier Serra-Picamal, S. Derzsi, E. Arwert, A. Weston, Víctor González-Tarragó, Alberto Elosegui-Artola, L. Albertazzi and 4 more. Nature Cell Biology, 2017

681 citations recorded by the source corpus.

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.

Subfields: Cell Biology, Orthopedics and Sports Medicine

View Paper: https://www.semanticscholar.org/paper/51bdfab60ab01f07f1bf41c4b8c6487a32c6829d

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Citations in the corpus

EMT subtype influences epithelial plasticity and mode of cell migration (2018, background): “…suggest that metastases can also arise from the collective migration and colonization of tumor cells (Aceto et al., 2014; Cheung and Ewald, 2016; Friedl et al., 2012; Haeger et al., 2015; Labernadie et al., 2017; Maddipati and Stanger, 2015) and may not require E-cadherin loss (Liu et al., 2014a).”