Caveolin-1-Mediated Tumor Suppression Is Linked to Reduced HIF1α S-Nitrosylation and Transcriptional Activity in Hypoxia

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dc.contributor.authorSanhueza, Carlos
dc.contributor.authorCastillo Bennett, Jimena
dc.contributor.authorValenzuela-Valderrama, Manuel
dc.contributor.authorContreras, Pamela
dc.contributor.authorLobos-González, Lorena
dc.contributor.authorCampos, América
dc.contributor.authorWehinger, Sergio
dc.contributor.authorLladser, Álvaro
dc.contributor.authorKiessling, Rolf
dc.contributor.authorLeyton, Lisette
dc.contributor.authorQuest, Andrew F. G.
dc.date.accessioned2021-07-13T16:23:41Z
dc.date.available2021-07-13T16:23:41Z
dc.date.issued2020
dc.description.abstractCaveolin-1 (CAV1) is a well-established nitric oxide synthase inhibitor, whose function as a tumor suppressor is favored by, but not entirely dependent on, the presence of E-cadherin. Tumors are frequently hypoxic and the activation of the hypoxia-inducible factor-1α (HIF1α) promotes tumor growth. HIF1α is regulated by several post-translational modifications, including S-nitrosylation. Here, we evaluate the mechanisms underlying tumor suppression by CAV1 in cancer cells lacking E-cadherin in hypoxia. Our main findings are that CAV1 reduced HIF activity and Vascular Endothelial Growth Factor expression in vitro and in vivo. This effect was neither due to reduced HIF1α protein stability or reduced nuclear translocation. Instead, HIF1α S-nitrosylation observed in hypoxia was diminished by the presence of CAV1, and nitric oxide synthase (NOS) inhibition by Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) reduced HIF1α transcriptional activity in cells to the same extent as observed upon CAV1 expression. Additionally, arginase inhibition by (S)-(2-Boronoethyl)-L-cysteine (BEC) partially rescued cells from the CAV1-mediated suppression of HIF1α transcriptional activity. In vivo, CAV1-mediated tumor suppression was dependent on NOS activity. In summary, CAV1-dependent tumor suppression in the absence of E-cadherin is linked to reduced HIF1α transcriptional activity via diminished NOS-mediated HIF1α S-nitrosylation.es
dc.format.extent18 p.es
dc.identifier.citationCancers (Basel) . 2020 Aug 20;12(9):2349es
dc.identifier.urihttps://doi.org/10.3390/cancers12092349es
dc.identifier.urihttp://hdl.handle.net/11447/4162
dc.language.isoenes
dc.subjectHIF1αes
dc.subjectS-nitrosylationes
dc.subjectVEGFes
dc.subjectCaveolin-1es
dc.subjectHypoxiaes
dc.subjectTumor suppressiones
dc.titleCaveolin-1-Mediated Tumor Suppression Is Linked to Reduced HIF1α S-Nitrosylation and Transcriptional Activity in Hypoxiaes
dc.typeArticlees

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