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

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dc.contributor.authorDíaz-Valdivia, N.I.
dc.contributor.authorCalderón, C.C.
dc.contributor.authorDíaz, J.E.
dc.contributor.authorLobos-González, L.
dc.contributor.authorSepulveda, H.
dc.contributor.authorOrtíz, R.J.
dc.contributor.authorMartinez, S.
dc.contributor.authorSilva, V.
dc.contributor.authorMaldonado, H.J.
dc.contributor.authorSilva, P.
dc.contributor.authorWehinger, S.
dc.contributor.authorBurzio, V.A.
dc.contributor.authorTorres, V.A.
dc.contributor.authorMontecino, M.
dc.contributor.authorLeyton, L.
dc.contributor.authorQuest, A.F.G.
dc.date.accessioned2018-06-26T15:08:59Z
dc.date.available2018-06-26T15:08:59Z
dc.date.issued2017
dc.descriptionIndexación: Scopus.es_ES
dc.description.abstractExpression 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.es_ES
dc.description.urihttp://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=22955&path[]=72439
dc.identifier.citationOncotarget, 8(67), pp. 111943-111965.es_ES
dc.identifier.issn1949-2553
dc.identifier.otherDOI: 10.18632/oncotarget.22955
dc.identifier.urihttp://repositorio.unab.cl/xmlui/handle/ria/6193
dc.language.isoenes_ES
dc.publisherImpact Journals LLCes_ES
dc.rights.licenseAttribution 3.0 Unported (CC BY 3.0)
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/
dc.subjectCaveolin-1es_ES
dc.subjectCell signalinges_ES
dc.subjectChemotherapyes_ES
dc.subjectEpigenetic silencinges_ES
dc.subjectReactive oxygen specieses_ES
dc.titleAnti-neoplastic drugs increase caveolin-1-dependent migration, invasion and metastasis of cancer cellses_ES
dc.typeArtículoes_ES
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