Unknown

Dataset Information

0

Integrin endosomal signalling suppresses anoikis.


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.

SUBMITTER: Alanko J 

PROVIDER: S-EPMC4890650 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

Integrin endosomal signalling suppresses anoikis.

Alanko Jonna J   Mai Anja A   Jacquemet Guillaume G   Schauer Kristine K   Kaukonen Riina R   Saari Markku M   Goud Bruno B   Ivaska Johanna J  

Nature cell biology 20151005 11


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. W  ...[more]