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dc.contributor.authorCasaburi, Ien
dc.contributor.authorAvena, Pen
dc.contributor.authorDe Luca, Aen
dc.contributor.authorChimento, Aen
dc.contributor.authorSirianni, Ren
dc.contributor.authorMalivindi, Ren
dc.contributor.authorRago, Ven
dc.contributor.authorFiorillo, Men
dc.contributor.authorDomanico, Fen
dc.contributor.authorCampana, Cen
dc.contributor.authorCappello, Aen
dc.contributor.authorSotgia, Federicaen
dc.contributor.authorLisanti, Michael Pen
dc.contributor.authorPezzi, Ven
dc.date.accessioned2015-10-02T11:45:23Zen
dc.date.available2015-10-02T11:45:23Zen
dc.date.issued2015-07-29en
dc.identifier.citationEstrogen Related Receptor α (ERRα) a Promising Target for the Therapy of Adrenocortical Carcinoma (ACC). 2015: Oncotargeten
dc.identifier.issn1949-2553en
dc.identifier.pmid26312764en
dc.identifier.urihttp://hdl.handle.net/10541/579073en
dc.description.abstractThe pathogenesis of the adrenocortical cancer (ACC) involves integration of molecular signals and the interplay of different downstream pathways (i.e. IGFII/IGF1R, β-catenin, Wnt, ESR1). This tumor is characterized by limited therapeutic options and unsuccessful treatments. A useful strategy to develop an effective therapy for ACC is to identify a common downstream target of these multiple pathways. A good candidate could be the transcription factor estrogen-related receptor alpha (ERRα) because of its ability to regulate energy metabolism, mitochondrial biogenesis and signalings related to cancer progression.In this study we tested the effect of ERRα inverse agonist, XCT790, on the proliferation of H295R adrenocortical cancer cell line. Results from in vitro and in vivo experiments showed that XCT790 reduced H295R cell growth. The inhibitory effect was associated with impaired cell cycle progression which was not followed by any apoptotic event. Instead, incomplete autophagy and cell death by a necrotic processes, as a consequence of the cell energy failure, induced by pharmacological reduction of ERRα was evidenced.Our results indicate that therapeutic strategies targeting key factors such as ERRα that control the activity and signaling of bioenergetics processes in high-energy demanding tumors could represent an innovative/alternative therapy for the treatment of ACC.
dc.languageENGen
dc.language.isoenen
dc.rightsArchived with thanks to Oncotargeten
dc.titleEstrogen Related Receptor α (ERRα) a promising target for the therapy of adrenocortical carcinoma (ACC).en
dc.typeArticleen
dc.contributor.departmentDepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria, Italyen
dc.identifier.journalOncotargeten
html.description.abstractThe pathogenesis of the adrenocortical cancer (ACC) involves integration of molecular signals and the interplay of different downstream pathways (i.e. IGFII/IGF1R, β-catenin, Wnt, ESR1). This tumor is characterized by limited therapeutic options and unsuccessful treatments. A useful strategy to develop an effective therapy for ACC is to identify a common downstream target of these multiple pathways. A good candidate could be the transcription factor estrogen-related receptor alpha (ERRα) because of its ability to regulate energy metabolism, mitochondrial biogenesis and signalings related to cancer progression.In this study we tested the effect of ERRα inverse agonist, XCT790, on the proliferation of H295R adrenocortical cancer cell line. Results from in vitro and in vivo experiments showed that XCT790 reduced H295R cell growth. The inhibitory effect was associated with impaired cell cycle progression which was not followed by any apoptotic event. Instead, incomplete autophagy and cell death by a necrotic processes, as a consequence of the cell energy failure, induced by pharmacological reduction of ERRα was evidenced.Our results indicate that therapeutic strategies targeting key factors such as ERRα that control the activity and signaling of bioenergetics processes in high-energy demanding tumors could represent an innovative/alternative therapy for the treatment of ACC.


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