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Estrogen related receptor α (ERRα) a promising target for the therapy of adrenocortical carcinoma (ACC)

Casaburi, I; Avena, P; De Luca, A; Chimento, A; Sirianni, R; Malivindi, R; Rago, V; Fiorillo, M; Domanico, F; Campana, C; Cappello, A; Sotgia, Federica; Lisanti, MP; Pezzi, V

Estrogen related receptor α (ERRα) a promising target for the therapy of adrenocortical carcinoma (ACC) Thumbnail


Authors

I Casaburi

P Avena

A De Luca

A Chimento

R Sirianni

R Malivindi

V Rago

M Fiorillo

F Domanico

C Campana

A Cappello

V Pezzi



Abstract

The 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.

Citation

Casaburi, I., Avena, P., De Luca, A., Chimento, A., Sirianni, R., Malivindi, R., …Pezzi, V. (2015). Estrogen related receptor α (ERRα) a promising target for the therapy of adrenocortical carcinoma (ACC). Oncotarget, 6(28), 25135-25148. https://doi.org/10.18632/oncotarget.4722

Journal Article Type Article
Acceptance Date Jul 17, 2015
Publication Date Jul 29, 2015
Deposit Date Jun 29, 2016
Publicly Available Date Jun 29, 2016
Journal Oncotarget
Electronic ISSN 1949-2553
Publisher Impact Journals
Volume 6
Issue 28
Pages 25135-25148
DOI https://doi.org/10.18632/oncotarget.4722
Publisher URL http://dx.doi.org/10.18632/oncotarget.4722
Related Public URLs http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=index
Additional Information Funders : Funder not known

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