Inhibition of glycolysis and Src/Akt signaling reduces Caveolin-1-enhanced metastasis

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dc.contributor.authorSimón, Layla
dc.contributor.authorTorres, Keila
dc.contributor.authorContreras, Pamela
dc.contributor.authorDiaz-Valdivia, Natalia
dc.contributor.authorLeyton, Lisette
dc.contributor.authorQuest, Andrew F. G.
dc.date.accessioned2024-11-26T14:42:22Z
dc.date.available2024-11-26T14:42:22Z
dc.date.issued2024-06-03
dc.description.abstractMetastasis is the leading cause of cancer-related deaths, making the development of novel, more effective therapies imperative to alleviate patient suffering. Metabolic switching is a hallmark of cancer cells that facilitates metastasis. Cancer cells obtain most of their energy and intermediate metabolites, which are required to proliferate and metastasize, through aerobic glycolysis. Previous work from our laboratory has shown that Caveolin-1 (CAV1) expression in cancer cells promotes glycolysis and metastasis. Here, we sought to determine if limiting glycolysis reduced CAV1-enhanced metastasis and to identify the mechanism(s) involved. We evaluated the effects of the glycolysis inhibitor 2-deoxy-D-glucose (2-DG) in metastatic melanoma and breast cancer cell lines expressing or not CAV1. Non-cytotoxic concentrations of 2-DG (1 mM) inhibited the migration of B16-F10 melanoma and MDA-MB-231 breast cancer cells. CAV1-mediated activation of Src/Akt signaling was required for CAV1-enhanced migration and was blocked in the presence of 2-DG. Moreover, inhibition of Akt reduced CAV1-enhanced lung metastasis of B16-F10 cells. Collectively, these findings highlight the importance of CAV1-induced metabolic reprogramming for metastasis and point towards possible therapeutic approaches to prevent metastatic disease by inhibiting glycolysis and Src/Akt signaling.
dc.identifier.citationBiomedicine and Pharmacotherapy, Vol. 176, N° 116841 (2024) p. 1-11.
dc.identifier.doihttps://doi.org/10.1016/j.biopha.2024.116841
dc.identifier.issn0753-3322
dc.identifier.issne1950-6007
dc.identifier.orcidhttps://orcid.org/0000-0002-0130-3519
dc.identifier.urihttp://hdl.handle.net/20.500.12254/3912
dc.language.isoen
dc.publisherElsevier
dc.rightsAtribución-NoComercial-CompartirIgual 3.0 Chile (CC BY-NC-SA 3.0 CL)
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/cl/
dc.subjectMetabolic switch
dc.subjectMelanoma
dc.subjectMigration
dc.subjectGlycolysis inhibitor
dc.subjectDasitinib
dc.subjectBreast cancer
dc.titleInhibition of glycolysis and Src/Akt signaling reduces Caveolin-1-enhanced metastasis
dc.typeArticle
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