title: Integrin endosomal signalling suppresses anoikis.
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.
authors.affiliation: Turku Centre for Biotechnology, University of Turku, Turku FIN-20520, Finland.|VTT Technical Research Centre of Finland, Turku FIN-20520, Finland.
authors.forename: Jonna
authors.initials: J
authors.lastname: Alanko
authors.affiliation: Turku Centre for Biotechnology, University of Turku, Turku FIN-20520, Finland.
authors.forename: Anja
authors.initials: A
authors.lastname: Mai
authors.affiliation: Turku Centre for Biotechnology, University of Turku, Turku FIN-20520, Finland.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Jacquemet
authors.affiliation: Molecular Mechanisms of Intracellular Transport, Institut Curie, Paris 75248, France.
authors.forename: Kristine
authors.initials: K
authors.lastname: Schauer
authors.affiliation: Turku Centre for Biotechnology, University of Turku, Turku FIN-20520, Finland.
authors.forename: Riina
authors.initials: R
authors.lastname: Kaukonen
authors.affiliation: Turku Centre for Biotechnology, University of Turku, Turku FIN-20520, Finland.|VTT Technical Research Centre of Finland, Turku FIN-20520, Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Saari
authors.affiliation: Molecular Mechanisms of Intracellular Transport, Institut Curie, Paris 75248, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Goud
authors.affiliation: Turku Centre for Biotechnology, University of Turku, Turku FIN-20520, Finland.|VTT Technical Research Centre of Finland, Turku FIN-20520, Finland.|Department of Biochemistry and Food Chemistry, University of Turku, Turku FIN-20520, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Ivaska
mesh_terms: D000818:Animals; D023102:Anoikis / Q000235:genetics / Q000502:physiology*; D016466:CHO Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004705:Endocytosis / Q000235:genetics / Q000502:physiology; D011992:Endosomes / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D010766:Phosphorylation; D011485:Protein Binding; D034622:RNA Interference; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D020691:rab GTP-Binding Proteins / Q000378:metabolism
chemical_list: D019012:Integrin beta1; D051417:Focal Adhesion Kinase 1; D020691:rab GTP-Binding Proteins