Lan B. Hoang -Minh
University of Florida, USA
Title: Key roles of mitochondrial function and lipid metabolism in slow-cycling glioblastoma cells
Biography
Biography: Lan B. Hoang -Minh
Abstract
Malignancies oft en exhibit rewired metabolism in order to satisfy the major energy and biosynthesis requirements of rapidly growing tumors. Despite the presence of suffi cient oxygen in their environment, tumors frequently exhibit elevated glycolysis. Th is metabolic reprogramming to glycolysis, known as the Warburg phenomenon, has commonly been associated with an impairment of mitochondrial function, thus restricting the metabolism of alternative substrates and limiting tumor cells’ metabolic diversity and adaptation. Here, we demonstrate that glioblastoma (GBM) tumor cells display metabolic heterogeneity, with fast-cycling cells harnessing anaerobic glycolysis and slow- cycling cells oxidative metabolism to support their growth and survival. We report the existence of SCCs in GBM, cells that display migration, invasion, and chemoresistance characteristics that might underlie tumor recurrence. SCCs consistently demonstrate heightened mitochondrial respiration activity as well as increased fatty acid metabolism. In addition, SCCs are more sensitive to inhibition of oxidative phosphorylation than to glucose deprivation, in vitro and in a murine xenograft model of GBM, and targeting both oxidative phosphorylation and the glycolytic pathway has a combinatorial inhibitory eff ect on GBM cell viability. Th ese results demonstrate the presence of cellular subpopulations that exhibit distinct metabolic activities in GBM and highlight the importance of comprehensive metabolic inhibition in the novel GBM treatment strategies.