Integrin endosomal signalling suppresses anoikis




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

PublisherNATURE PUBLISHING GROUP

2015

Nature Cell Biology

NATURE CELL BIOLOGY

NAT CELL BIOL

17

11

1412

1421

10

1465-7392

DOIhttps://doi.org/10.1038/ncb3250(external)



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 2024-26-11 at 23:14