[BIO Colloquium] Metabolic Reprogramming in Cancer
  • Young Chan Chae, Ph.D.(The Wistar Institute, USA)
  • SLS Colloquia / Oct 21th 04:00 pm / AMRB 113
Abstract
The metabolism of cancer cells is reprogrammed to support macromolecular synthesis needed for cell growth. These alterations are crucial for adaptation of tumor cells to constantly changing intra- and extracellular environments, such as hypoxia, glucose limitation, and acidosis, but the wirings of this process are still largely elusive. Here, we show that chaperones compartmentalized in mitochondria are required for regulation of tumor bioenergetics, adaptation to cellular stress and cell survival. Interference with this process activates a signaling network that involves phosphorylation of nutrient-sensing AMP-activated kinase (AMPK), inhibition of rapamycin-sensitive mTOR complex 1 (mTORC1), induction of autophagy, and expression of an endoplasmic reticulum (ER) unfolded protein response (UPR). Furthermore, metabolic reprogramming supports chemoresistance and inhibition of mitochondrial chaperones efficiently prevent chemoresistance. Finally, this signaling network confers a survival and proliferative advantage to genetically disparate tumors, and correlates with worse outcome in cancer patients.