Anti-neoplastic drugs increase caveolin-1-dependent migration, invasion and metastasis of cancer cells

ONCOTARGET

dc.creatorDíaz-Valdivia, Natalia Isabel
dc.creatorCalderón, Claudia C
dc.creatorDíaz, Jorge E
dc.creatorLobos-González, Lorena
dc.creatorSepúlveda, Hugo
dc.creatorOrtiz, Rina J
dc.creatorMartínez, Samuel
dc.creatorSilva, Verónica
dc.creatorMaldonado-Lorca, Horacio J
dc.creatorSilva, Patricio
dc.creatorWehinger, Sergio
dc.creatorBurzio, Verónica A
dc.creatorTorres, Vicente A
dc.creatorMontecino, Martín
dc.creatorLeyton-Campos, Lisette
dc.creatorQuest, Andrew F G
dc.date2021-08-23T22:51:12Z
dc.date2022-07-08T20:28:27Z
dc.date2021-08-23T22:51:12Z
dc.date2022-07-08T20:28:27Z
dc.date2017
dc.date.accessioned2023-08-22T08:04:26Z
dc.date.available2023-08-22T08:04:26Z
dc.identifier1150744
dc.identifier1150744
dc.identifierhttps://hdl.handle.net/10533/250742
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8332966
dc.descriptionExpression of the scaffolding protein Caveolin-1 (CAV1) enhances migration and invasion of metastatic cancer cells. Yet, CAV1 also functions as a tumor suppressor in early stages of cancer, where expression is suppressed by epigenetic mechanisms. Thus, we sought to identify stimuli/ mechanisms that revert epigenetic CAV1 silencing in cancer cells and evaluate how this affects their metastatic potential. We reasoned that restricted tissue availability of anti-neoplastic drugs during chemotherapy might expose cancer cells to sub-therapeutic concentrations, which activate signaling pathways and the expression of CAV1 to favor the acquisition of more aggressive traits. Here, we used in vitro [2D, invasion] and in vivo (metastasis) assays, as well as genetic and biochemical approaches to address this question. Colon and breast cancer cells were identified where CAV1 levels were low due to epigenetic suppression and could be reverted by treatment with the methyltransferase inhibitor 5'-azacytidine. Exposure of these cells to anti-neoplastic drugs for short periods of time (24-48 h) increased CAV1 expression through ROS production and MEK/ ERK activation. In colon cancer cells, increased CAV1 expression enhanced migration and invasion in vitro via pathways requiring Src-family kinases, as well as Rac-1 activity. Finally, elevated CAV1 expression in colon cancer cells following exposure in vitro to sub-cytotoxic drug concentrations increased their metastatic potential in vivo. Therefore exposure of cancer cells to anti-neoplastic drugs at non-lethal drug concentrations induces signaling events and changes in transcription that favor CAV1-dependent migration, invasion and metastasis. Importantly, this may occur in the absence of selection for drug-resistance.
dc.descriptionRegular 2015
dc.descriptionFONDECYT
dc.descriptionFONDECYT
dc.languageeng
dc.relationhandle/10533/111557
dc.relationhandle/10533/111541
dc.relationhandle/10533/108045
dc.relationhttps://doi.org/10.18632/oncotarget.22955
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 Chile
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.rightsinfo:eu-repo/semantics/article
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleAnti-neoplastic drugs increase caveolin-1-dependent migration, invasion and metastasis of cancer cells
dc.titleONCOTARGET
dc.typeArticulo
dc.typeinfo:eu-repo/semantics/publishedVersion


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