Integrin endosomal signalling suppresses anoikis.

Alanko, Mai, Guillaume Jacquemet, Schauer, Kaukonen, Saari, Goud, Ivaska

Research output: Contribution to journalArticleScientificpeer-review

100 Citations (Scopus)

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.
Original languageUndefined/Unknown
Pages (from-to)1412–21
JournalNature Cell Biology
Volume17
Issue number11
DOIs
Publication statusPublished - 2015
MoE publication typeA1 Journal article-refereed

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