期刊
NATURE CELL BIOLOGY
卷 17, 期 11, 页码 1412-1421出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb3250
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资金
- Academy of Finland
- ERC Starting Grant
- ERC Consolidator Grant
- Sigrid Juselius Foundation
- Finnish Cancer Organization
- Turku Doctoral Program of Biomedical Sciences
- EMBO Short-Term Fellowship
- EMBO Long-Term Fellowship
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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