title: Caveolin-1-enhanced motility and focal adhesion turnover require tyrosine-14 but not accumulation to the rear in metastatic cancer cells.
abstract: Caveolin-1 is known to promote cell migration, and increased caveolin-1 expression is associated with tumor progression and metastasis. In fibroblasts, caveolin-1 polarization and phosphorylation of tyrosine-14 are essential to promote migration. However, the role of caveolin-1 in migration of metastatic cells remains poorly defined. Here, caveolin-1 participation in metastatic cell migration was evaluated by shRNA targeting of endogenous caveolin-1 in MDA-MB-231 human breast cancer cells and ectopic expression in B16-F10 mouse melanoma cells. Depletion of caveolin-1 in MDA-MB-231 cells reduced, while expression in B16-F10 cells promoted migration, polarization and focal adhesion turnover in a sequence of events that involved phosphorylation of tyrosine-14 and Rac-1 activation. In B16-F10 cells, expression of a non-phosphorylatable tyrosine-14 to phenylalanine mutant failed to recapitulate the effects observed with wild-type caveolin-1. Alternatively, treatment of MDA-MB-231 cells with the Src family kinase inhibitor PP2 reduced caveolin-1 phosphorylation on tyrosine-14 and cell migration. Surprisingly, unlike for fibroblasts, caveolin-1 polarization and re-localization to the trailing edge were not observed in migrating metastatic cells. Thus, expression and phosphorylation, but not polarization of caveolin-1 favor the highly mobile phenotype of metastatic cells.
authors.affiliation: Laboratory of Cellular Communication, Center for Molecular Studies of the Cell, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
authors.forename: Hery
authors.initials: H
authors.lastname: Urra
authors.forename: Vicente A
authors.initials: VA
authors.lastname: Torres
authors.forename: Rina J
authors.initials: RJ
authors.lastname: Ortiz
authors.forename: Lorena
authors.initials: L
authors.lastname: Lobos
authors.forename: María I
authors.initials: MI
authors.lastname: Díaz
authors.forename: Natalia
authors.initials: N
authors.lastname: Díaz
authors.forename: Steffen
authors.initials: S
authors.lastname: Härtel
authors.forename: Lisette
authors.initials: L
authors.lastname: Leyton
authors.forename: Andrew F G
authors.initials: AF
authors.lastname: Quest
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D051381:Rats; D014443:Tyrosine / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D051242:Caveolin 1; D014443:Tyrosine; D019061:src-Family Kinases; D054460:rho-Associated Kinases; D020558:GTP Phosphohydrolases