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Alanko J
; Mai A
; Jacquemet G
; Schauer K
; Kaukonen R
; Saari M
; Goud B
; Ivaska J
Nat Cell Biol
2015[Nov]; 17
(11
): 1412-21
PMID26436690
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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.
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