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.

journal_name

Nat Cell Biol

journal_title

Nature cell biology

authors

Alanko J,Mai A,Jacquemet G,Schauer K,Kaukonen R,Saari M,Goud B,Ivaska J

doi

10.1038/ncb3250

subject

Has Abstract

pub_date

2015-11-01 00:00:00

pages

1412-21

issue

11

eissn

1465-7392

issn

1476-4679

pii

ncb3250

journal_volume

17

pub_type

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