RT Journal Article
T1 The antioxidant uncoupling protein 2 stimulates hnRNPA2/B1, GLUT1 and PKM2 expression and sensitizes pancreas cancer cells to glycolysis inhibition
A1 Brandi, Jessica
A1 Cecconi, Daniela
A1 Cordani, Marco
A1 Torrens-Mas, Margalida
A1 Pacchiana, Raffaella
A1 Dalla Pozza, Elisa
A1 Butera, Giovanna
A1 Manfredi, Marcello
A1 Marengo, Emilio
A1 Oliver, Jordi
A1 Roca, Pilar
A1 Dando, Ilaria
A1 Massimo, Donadelli
AB Several evidence indicate that metabolic alterations play a pivotal role in cancer development. Here, we report that the mitochondrial uncoupling protein 2 (UCP2) sustains the metabolic shift from mitochondrial oxidative phosphorylation (mtOXPHOS) to glycolysis in pancreas cancer cells. Indeed, we show that UCP2 sensitizes pancreas cancer cells to the treatment with the glycolytic inhibitor 2-deoxy-D-glucose. Through a bidimensional electrophoresis analysis, we identify 19 protein species differentially expressed after treatment with the UCP2 inhibitor genipin and, by bioinformatic analyses, we show that these proteins are mainly involved in metabolic processes. In particular, we demonstrate that the antioxidant UCP2 induces the expression of hnRNPA2/B1, which is involved in the regulation of both GLUT1 and PKM2 mRNAs, and of lactate dehydrogenase (LDH) increasing the secretion of L-lactic acid. We further demonstrate that the radical scavenger N-acetyl-L-cysteine reverts hnRNPA2/B1 and PKM2 inhibition by genipin indicating a role for reactive oxygen species in the metabolic reprogramming of cancer cells mediated by UCP2. We also observe an UCP2-dependent decrease in mtOXPHOS complex I (NADH dehydrogenase), complex IV (cytochrome c oxidase), complex V (ATPase) and in mitochondrial oxygen consumption, suggesting a role for UCP2 in the counteraction of pancreatic cancer cellular respiration. All these results reveal novel mechanisms through which UCP2 promotes cancer cell proliferation with the concomitant metabolic shift from mtOXPHOS to the glycolytic pathway.
PB Elsevier
SN 0891-5849
YR 2016
FD 2016
LK https://hdl.handle.net/20.500.14352/97834
UL https://hdl.handle.net/20.500.14352/97834
LA eng
NO Brandi, Jessica, et al. «The Antioxidant Uncoupling Protein 2 Stimulates hnRNPA2/B1, GLUT1 and PKM2 Expression and Sensitizes Pancreas Cancer Cells to Glycolysis Inhibition». Free Radical Biology and Medicine, vol. 101, diciembre de 2016, pp. 305-16. https://doi.org/10.1016/j.freeradbiomed.2016.10.499.
NO University of Verona
NO Instituto de Salud Carlos III
NO European Commission
NO Umberto Veronesi Foundation
NO Ministerio de Educación, Cultura y Deporte (España)
DS Docta Complutense
RD 18 abr 2025