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

Ivan Casaburi, Paola Avena, Arianna De Luca, Adele Chimento, Rosa Sirianni, Rocco Malivindi, Vittoria Rago, Marco Fiorillo, Francesco Domanico, Carmela Campana, Anna Rita Cappello, Federica Sotgia, Michael P. Lisanti, Vincenzo Pezzi

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The pathogenesis of the adrenocortical cancer (ACC) involves integration of molecular signals and the interplay of different downstream pathways (i.e. IGFII/ IGF1R, ß-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 (ERRa) because of its ability to regulate energy metabolism, mitochondrial biogenesis and signalings related to cancer progression. In this study we tested the effect of ERRa 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 ERRa was evidenced. Our results indicate that therapeutic strategies targeting key factors such as ERRa that control the activity and signaling of bioenergetics processes in highenergy demanding tumors could represent an innovative/alternative therapy for the treatment of ACC.

Original languageEnglish (US)
Pages (from-to)25135-25148
Number of pages14
JournalOncotarget
Volume6
Issue number28
DOIs
StatePublished - 2015

Keywords

  • ATP depletion
  • Adrenocortical cancer
  • ERRa
  • Mitochondria

ASJC Scopus subject areas

  • Oncology

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    Casaburi, I., Avena, P., De Luca, A., Chimento, A., Sirianni, R., Malivindi, R., Rago, V., Fiorillo, M., Domanico, F., Campana, C., Cappello, A. R., Sotgia, F., Lisanti, M. P., & Pezzi, V. (2015). Estrogen related receptor a (ERRa) a promising target for the therapy of adrenocortical carcinoma (ACC). Oncotarget, 6(28), 25135-25148. https://doi.org/10.18632/oncotarget.4722