Integrin endosomal signalling suppresses anoikis

Jonna Alanko, Anja Mai, Guillaume Jacquemet, Kristine Schauer, Riina Kaukonen, Markku Saari, Bruno Goud, Johanna Ivaska

Research output: Contribution to journalArticleScientificpeer-review

83 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1412-1421
JournalNature Cell Biology
Volume17
DOIs
Publication statusPublished - 2015
MoE publication typeA1 Journal article-refereed

    Fingerprint

Keywords

  • cancer
  • cell adhesion
  • endosomes
  • integrin signalling

Cite this

Alanko, J., Mai, A., Jacquemet, G., Schauer, K., Kaukonen, R., Saari, M., Goud, B., & Ivaska, J. (2015). Integrin endosomal signalling suppresses anoikis. Nature Cell Biology, 17, 1412-1421. https://doi.org/10.1038/ncb3250