TY - JOUR
T1 - A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion
AU - Labernadie, Anna
AU - Kato, Takuya
AU - Brugués, Agustí
AU - Serra-Picamal, Xavier
AU - Derzsi, Stefanie
AU - Arwert, Esther
AU - Weston, Anne
AU - González-Tarragó, Victor
AU - Elosegui-Artola, Alberto
AU - Albertazzi, Lorenzo
AU - Alcaraz, Jordi
AU - Roca-Cusachs, Pere
AU - Sahai, Erik
AU - Trepat, Xavier
PY - 2017/3/1
Y1 - 2017/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85014184482&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85014184482&partnerID=8YFLogxK
U2 - 10.1038/ncb3478
DO - 10.1038/ncb3478
M3 - Article
C2 - 28218910
AN - SCOPUS:85014184482
SN - 1465-7392
VL - 19
SP - 224
EP - 237
JO - Nature Cell Biology
JF - Nature Cell Biology
IS - 3
ER -