IQUIBICEN   23947
INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CIENCIAS EXACTAS Y NATURALES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Heme-Oxygenase 1 drives the metabolic fate in prostate cancer
Autor/es:
VELAZQUEZ, FLORENCIA; LABANCA, ESTEFANIA; GUERON, GERALDINE; CASCARDO, FLORENCIA; ANSELMINO, NICOLAS; NAVONE, NORA; ANTICO ARCIUCH, VALERIA; LAGE VICKERS, SOFIA; COTIGNOLA, JAVIER; VAZQUEZ, ELBA
Lugar:
CABA
Reunión:
Congreso; Reunión Conjunta de Sociedades de BioCiencias - LXII Reunion Anual SAIC; 2017
Institución organizadora:
Sociedad Argentina de Investigacion Clinica
Resumen:
Prostate cancer (PCa) is the second leading cause of cancer-associateddeath in men. 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 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 pharmacological induction (hemin treatment) or genetic induction of HO-1 in PC3 cells. STAR and ATP5L2 were 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 by Gene Ontology revealed alterations in several metabolic pathways such as steroid, proline and lipid metabolism, and ATP synthesis. Functional analysis highlighted a decrease in oxygen consumtion rate and ATP production under hemin treatment. Furthermore, HO-1 induction led to a decrease in the extracellular lactate levels. Bone is the only site of PCa progression, and bone cells are able to produce factors that favor progression. However, the molecular nature of this interaction remains elusive. Our results performed on co-cultures of PC3 cells (treated or not with hemin) with Raw264.7 (pre-osteoclastic) or MC3T3 (pre-osteoblastic) cells demonstrate that HO-1 directs the metabolic fate of bone precursor cells due to the deregulation of glycolytic genes. HO-1 induction in PC3 cells downregulated PKM2 and LDHA expression in co-cultured Raw264.7 and MC3T3 cells (p