| First Author | Labernadie A | Year | 2017 |
| Journal | Nat Cell Biol | Volume | 19 |
| Issue | 3 | Pages | 224-237 |
| PubMed ID | 28218910 | Mgi Jnum | J:250381 |
| Mgi Id | MGI:5920813 | Doi | 10.1038/ncb3478 |
| Citation | Labernadie A, et al. (2017) A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion. Nat Cell Biol 19(3):224-237 |
| abstractText | 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. |
