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Integrin endosomal signalling suppresses anoikis
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Journal Article
Integrin endosomal signalling suppresses anoikis
2015
Overview
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.
Ivaska and colleagues report that endocytosed integrins are able to signal from endosomes in an FAK-dependent manner. They further show that endosomal integrin signalling can promote anoikis resistance and lung colonization in cancer cells.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/31
/ 13/95
/ 14
/ 14/19
/ 631/67
/ Adhesion
/ Animals
/ Cellular signal transduction
/ Extracellular Matrix - metabolism
/ Focal Adhesion Kinase 1 - genetics
/ Focal Adhesion Kinase 1 - metabolism
/ Focal Adhesions - metabolism
/ Humans
/ rab GTP-Binding Proteins - metabolism
/ Signal Transduction - genetics
