Src-family kinase inhibitors block early steps of caveolin-1-enhanced lungmetastasis by melanoma cells

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dc.contributor.authorOrtiz, Rina
dc.contributor.authorDíaz, Jorge
dc.contributor.authorDíaz-Valdivia, Natalia
dc.contributor.authorMartínez, Samuel
dc.contributor.authorSimón, Layla
dc.contributor.authorContreras, Pamela
dc.contributor.authorLobos-González, Lorena
dc.contributor.authorGuerrero, Simón
dc.contributor.authorLeyton, Lisette
dc.contributor.authorQuest, Andrew F.G.
dc.date.accessioned2021-07-12T15:28:00Z
dc.date.available2021-07-12T15:28:00Z
dc.date.issued2020
dc.description.abstractIn advanced stages of cancer disease, caveolin-1 (CAV1) expression increases and correlates with increased migratory and invasive capacity of the respective tumor cells. Previous findings from our laboratory revealed that specific ECM-integrin interactions and tyrosine-14 phosphorylation of CAV1 are required for CAV1-enhanced melanoma cell migration, invasion and metastasis in vivo. In this context, CAV1 phosphorylation on tyrosine-14 mediated by non-receptor Src-family tyrosine kinases seems to be important; however, the effect of Src-family kinase inhibitors on CAV1-enhanced metastasis in vivo has not been studied. Here, we evaluated the effect of CAV1 and c-Abl overexpression, as well as the use of the Src-family kinase inhibitors, PP2 and dasatinib (more specific for Src/Abl) in lung metastasis of B16F10 melanoma cells. Overexpression of CAV1 and c-Abl enhanced CAV1 phosphorylation and the metastatic potential of the B16F10 murine melanoma cells. Alternatively, treatment with PP2 or dasatinib for 2 h reduced CAV1 tyrosine-14 phosphorylation and levels recovered fully within 12 h of removing the inhibitors. Nonetheless, pre-treatment of cells with these inhibitors for 2 h sufficed to prevent migration, invasion and trans-endothelial migration in vitro. Importantly, the transient decrease in CAV1 phosphorylation by these kinase inhibitors prevented early steps of CAV1-enhanced lung metastasis by B16F10 melanoma cells injected into the tail vein of mice. In conclusion, this study underscores the relevance of CAV1 tyrosine-14 phosphorylation by Src-family kinases during the first steps of the metastatic sequence promoted by CAV1. These findings open up potential options for treatment of metastatic tumors in patients in which Src-family kinase activation and CAV1 overexpression favor dissemination of cancer cells to secondary sites.es
dc.format.extent13 p.es
dc.identifier.citationBiochemical Pharmacology Volume 177, July 2020, 113941es
dc.identifier.urihttps://doi.org/10.1016/j.bcp.2020.113941es
dc.identifier.urihttp://hdl.handle.net/11447/4143
dc.language.isoenes
dc.subjectSrc-family kinase inhibitorses
dc.subjectPhospho-caveolin-1es
dc.subjectMigrationes
dc.subjectMetastasises
dc.subjectMelanomaes
dc.titleSrc-family kinase inhibitors block early steps of caveolin-1-enhanced lungmetastasis by melanoma cellses
dc.typeArticlees

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