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

75 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

Anoikis
Integrins
Focal Adhesion Protein-Tyrosine Kinases
Endosomes
Endocytosis
Cell Adhesion
Cell Membrane
Focal Adhesions
Monomeric GTP-Binding Proteins
Cell Survival

Keywords

  • cancer
  • cell adhesion
  • endosomes
  • integrin signalling

Cite this

Alanko, J., Mai, A., Jacquemet, G., Schauer, K., Kaukonen, R., Saari, M., ... Ivaska, J. (2015). Integrin endosomal signalling suppresses anoikis. Nature Cell Biology, 17, 1412-1421. https://doi.org/10.1038/ncb3250
Alanko, Jonna ; Mai, Anja ; Jacquemet, Guillaume ; Schauer, Kristine ; Kaukonen, Riina ; Saari, Markku ; Goud, Bruno ; Ivaska, Johanna. / Integrin endosomal signalling suppresses anoikis. In: Nature Cell Biology. 2015 ; Vol. 17. pp. 1412-1421.
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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, vol. 17, pp. 1412-1421. https://doi.org/10.1038/ncb3250

Integrin endosomal signalling suppresses anoikis. / Alanko, Jonna; Mai, Anja; Jacquemet, Guillaume; Schauer, Kristine; Kaukonen, Riina; Saari, Markku; Goud, Bruno; Ivaska, Johanna.

In: Nature Cell Biology, Vol. 17, 2015, p. 1412-1421.

Research output: Contribution to journalArticleScientificpeer-review

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T1 - Integrin endosomal signalling suppresses anoikis

AU - Alanko, Jonna

AU - Mai, Anja

AU - Jacquemet, Guillaume

AU - Schauer, Kristine

AU - Kaukonen, Riina

AU - Saari, Markku

AU - Goud, Bruno

AU - Ivaska, Johanna

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AB - 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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Alanko J, Mai A, Jacquemet G, Schauer K, Kaukonen R, Saari M et al. Integrin endosomal signalling suppresses anoikis. Nature Cell Biology. 2015;17:1412-1421. https://doi.org/10.1038/ncb3250