Abstract B18: Metabolic signature characterization in prostate cancer mediated by Heme-oxygenase 1

Abstract

Abstract Prostate cancer (PCa) is the second leading cause of cancer-associated death in men, with bone metastases being the main cause of mortality. Energetic metabolism alterations have become a new hallmark of cancer, since variations in a single gene can orchestrate changes in metabolic pathways and confer an adaptive advantage. Heme-oxygenase 1 (HO-1) exerts an antitumoral role in PCa inhibiting cell proliferation, migration, tumor growth and angiogenesis. The aim of this work was to assess the role of HO-1 in the metabolic signature of PCa. Through RNA-Seq we found a set of metabolic genes deregulated under pharmacologic induction (hemin treatment) or genetic induction of HO-1 in PC3 cells. STAR and ATP5L2 were found upregulated, while HMGCS2, PRODH and ACOT12 were downregulated. These genes encode for steroid hormone metabolism, ATP synthesis, ketogenesis, proline and lipid metabolism. The analysis of the deregulated genes (2-fold) under HO-1 modulation by Gene Ontology revealed alterations in several metabolic pathways such as steroid, tyrosine and lipid metabolism, and ion transport. Bone is the only site of PCa progression, and bone cells are able to produce factors that increase the growth and survival of tumor cells favoring progression. However, the molecular nature of this interaction remains to be elucidated. Our preliminary results performed on cocultures of PC3 cells (treated or not with hemin) with Raw264.7 (pre-osteoclastic) or MC3T3 (preosteoblastic) cells demonstrate that HO-1 is able to direct the metabolic fate of bone precursor cells due to the deregulation of glycolytic genes. HO-1 induction in PC3 cells downregulated the expression of PKM2 and LDHA in cocultured Raw264.7 and MC3T3 cells (p< 0.05). Based on our results, we propose HO-1 as a key regulator of the metabolic status of PCa cells and a powerful mediator capable of redefining the metabolic signature of bone precursor cells, thus favoring the establishment of a less aggressive phenotype. Citation Format: Valeria G. Antico Arciuch, Nicolas Anselmino, Alejandra Paez, Florencia Cascardo, Javier Cotignola, Geraldine Gueron, Elba Vazquez. Metabolic signature characterization in prostate cancer mediated by Heme-oxygenase 1 [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B18.