Integrin endosomal signalling suppresses anoikis.

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Alanko, Mai, Jacquemet, Schauer, Kaukonen, Saari, Goud, Ivaska
Publication year: 2015
Journal: Nature Cell Biology
Journal acronym: Nat Cell Biol
Volume number: 17
Issue number: 11
Start page: 1412
End page: 21
ISSN: 1476-4679


Abstract

Integrin-containing focal adhesions transmit extracellular signals across the plasma membrane to modulate cell adhesion, signalling and survival. Although integrins are known to undergo continuous endo/exocytic traffic, the potential impact of endocytic traffic on integrin-induced signals is unknown. Here, we demonstrate that integrin signalling is not restricted to cell-ECM adhesions and identify an endosomal signalling platform that supports integrin signalling away from the plasma membrane. We show that active focal adhesion kinase (FAK), an established marker of integrin-ECM downstream signalling, localizes with active integrins on endosomes. Integrin endocytosis positively regulates adhesion-induced FAK activation, which is early endosome antigen-1 and small GTPase Rab21 dependent. FAK binds directly to purified endosomes and becomes activated on them, suggesting a role for endocytosis in enhancing distinct integrin downstream signalling events. Finally, endosomal integrin signalling contributes to cancer-related processes such as anoikis resistance, anchorage independence and metastasis.

Last updated on 2020-22-01 at 05:14