Androgen-Dependent Prostate Cancer Cells Reprogram Their Metabolic Signature upon GLUT1 Upregulation by Manganese Superoxide Dismutase
Isabel Quiros-Gonzalez,
Pedro Gonzalez-Menendez,
Juan C. Mayo,
David Hevia,
Francisco Artime-Naveda,
Sheila Fernandez-Vega,
Mario Fernandez-Fernandez,
Pablo Rodriguez-Gonzalez,
José I. Garcia-Alonso,
Rosa M. Sainz
Affiliations
Isabel Quiros-Gonzalez
Departamento de Morfologia y Biologia Celular, Instituto Universitario de Oncologia del Principado de Asturias (IUOPA), University of Oviedo, 33006 Oviedo, Spain
Pedro Gonzalez-Menendez
Institute de Genetique Moleculaire de Montpellier, University of Montpellier, CNRS, 34293 Montpellier, France
Juan C. Mayo
Departamento de Morfologia y Biologia Celular, Instituto Universitario de Oncologia del Principado de Asturias (IUOPA), University of Oviedo, 33006 Oviedo, Spain
David Hevia
Departamento de Morfologia y Biologia Celular, Instituto Universitario de Oncologia del Principado de Asturias (IUOPA), University of Oviedo, 33006 Oviedo, Spain
Francisco Artime-Naveda
Departamento de Morfologia y Biologia Celular, Instituto Universitario de Oncologia del Principado de Asturias (IUOPA), University of Oviedo, 33006 Oviedo, Spain
Sheila Fernandez-Vega
Departamento de Morfologia y Biologia Celular, Instituto Universitario de Oncologia del Principado de Asturias (IUOPA), University of Oviedo, 33006 Oviedo, Spain
Mario Fernandez-Fernandez
Departamento de Quimica Fisica y Analítica, Universidad de Oviedo, Julián Clavería 8, 33006 Oviedo, Spain
Pablo Rodriguez-Gonzalez
Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33001 Oviedo, Spain
José I. Garcia-Alonso
Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33001 Oviedo, Spain
Rosa M. Sainz
Departamento de Morfologia y Biologia Celular, Instituto Universitario de Oncologia del Principado de Asturias (IUOPA), University of Oviedo, 33006 Oviedo, Spain
Prostate cancer is the second leading cause of cancer in men across the globe. The prostate gland accounts for some unique glycolytic metabolic characteristics, which causes the metabolic features of prostate tumor initiation and progression to remain poorly characterized. The mitochondrial superoxide dismutase (SOD2) is one of the major redox metabolism regulators. This study points out SOD2 as one major regulator for both redox and glycolytic metabolism in prostate cancer. SOD2 overexpression increases glucose transporter GLUT-1 and glucose uptake. This is not an insulin-mediated effect and seems to be sex-dependent, being present in male mice only. This event concurs with a series of substantial metabolic rearrangements at cytoplasmic and mitochondrial level. A concomitant decrease in glycolytic and pentose phosphate activity, and an increase in electron transfer in the mitochondrial electronic chain, were observed. The Krebs Cycle is altered to produce amino-acid intermediates by decreasing succinate dehydrogenase. This in turn generates a 13-fold increase in the oncometabolite succinate. The protein energy sensor AMPK is decreased at basal and phosphorylated levels in response to glucose deprivation. Finally, preliminary results in prostate cancer patients indicate that glandular areas presenting high levels of SOD2 show a very strong correlation with GLUT-1 protein levels (R2 = 0.287 p-value < 0.0001), indicating that in patients there may exist an analogous phenomenon to those observed in cell culture and mice.
