Format

Send to

Choose Destination
Nat Cell Biol. 2015 Nov;17(11):1412-21. doi: 10.1038/ncb3250. Epub 2015 Oct 5.

Integrin endosomal signalling suppresses anoikis.

Author information

1
Turku Centre for Biotechnology, University of Turku, Turku FIN-20520, Finland.
2
VTT Technical Research Centre of Finland, Turku FIN-20520, Finland.
3
Molecular Mechanisms of Intracellular Transport, Institut Curie, Paris 75248, France.
4
Department of Biochemistry and Food Chemistry, University of Turku, Turku FIN-20520, Finland.

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.

Comment in

PMID:
26436690
PMCID:
PMC4890650
DOI:
10.1038/ncb3250
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center