The inflammatory cytokine TNF contributes with RAC3-induced malignant transformation

dc.contributor.authorMachado, Mileni Soares
dc.contributor.authorRosa, Francisco D.
dc.contributor.authorLira, María C.
dc.contributor.authorUrtreger, Alejandro J.
dc.contributor.authorRubio, María F.
dc.contributor.authorCostas, Mónica A.
dc.date.accessioned2019-04-02T05:58:34Z
dc.date.available2019-04-02T05:58:34Z
dc.date.issued2018-11-02
dc.description.abstractRAC3 is a coactivator of steroid receptors and NF-kB. It is usually overexpressed in several tumors, contributes to maintain cancer stem cells and also to induce them when is overexpressed in non-tumoral cells. In this work, we investigated whether the inflammatory cytokine TNF may contribute to the transforming effects of RAC3 overexpression in the non-tumoral HEK293 cell line. The study model included the HEK293 tumoral transformed cell line constitutively overexpressing RAC3 by stable transfection and control non-tumoral cells transfected with an empty vector. The HeLa and T47D tumoral cells that naturally overexpress RAC3 were used as positive control. We found that TNF potentiated RAC3-induced mesenchymal transition, involving an increased E-Cadherin downregulation, Vimentin and SNAIL upregulation and enhanced migratory behavior. Moreover, concerning the molecular mechanisms by which TNF potentiates the RAC3 transforming action, they involve the IKK activation, which in addition induced the -Catenin transactivation. Our results demonstrate that although RAC3 overexpression could be a signal strong enough to induce cancer stem cells, the inflammatory microenvironment may be playing a key role contributing to the migratory and invasive phenotype required for metastasis and cancer persistence.en
dc.identifier.issn1611-2156
dc.identifier.urihttp://hdl.handle.net/2003/37971
dc.identifier.urihttp://dx.doi.org/10.17877/DE290R-19956
dc.language.isoen
dc.relation.ispartofseriesEXCLI Journal;Vol. 17 2018
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectRAC3en
dc.subjectCancer stem cellsen
dc.subjectMesenchymal cellsen
dc.subjectTNF-malignant transformationen
dc.subject.ddc610
dc.titleThe inflammatory cytokine TNF contributes with RAC3-induced malignant transformationen
dc.typeText
dc.type.publicationtypearticle
dcterms.accessRightsopen access
eldorado.dnb.zdberstkatid2132560-1
eldorado.secondarypublicationtrue

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