Discovery of a novel glucose metabolism in cancer: The role of endoplasmic reticulum beyond glycolysis and pentose phosphate shunt

• DOI: 10.1038/srep25092
• Publication Date: 2016-04-28T09:34:43Z
• Authors: Cecilia Marini; Silvia Ravera; Ambra Buschiazzo; Giovanna Bianchi; Anna Maria Orengo; Silvia Bruno; Gianluca Bottoni; Laura Emionite; Fabio Pastorino; Elena Monteverde; Lucia Garaboldi; Roberto Martella; Barbara Salani; Davide Maggi; Mirco Ponzoni; Franco Fais; Lizzia Raffaghello; Gianmario Sambuceti
• Keywords: Warburg Effect; Carbohydrate Metabolism; Hexose

Abstract Cancer metabolism is characterized by an accelerated glycolytic rate facing reduced activity of oxidative phosphorylation. This “Warburg effect” represents a standard to diagnose and monitor tumor aggressiveness with 18 F-fluorodeoxyglucose whose uptake currently regarded as accurate index total glucose consumption. Studying cancer metabolic response respiratory chain inhibition metformin, we repeatedly observed reduction tracer marked increase in puzzling discordance brought us discover that preferentially accumulates within endoplasmic reticulum exploiting the catalytic function hexose-6-phosphate-dehydrogenase. Silencing enzyme expression decreased both consumption, caused severe energy depletion NADPH content without altering mitochondrial function. These data document existence unknown triggered hexose-6-phosphate-dehydrogenase cells. Besides its basic relevance, this finding can improve clinical diagnosis might represent potential target for therapy.