Abstract PL02-01: Isogenic tumors can utilize heterogeneous mechanisms of nutrient uptake

Abstract

Abstract An emerging feature of cancer cell metabolism is the ability to acquire the anabolic precursors necessary to support cell viability and growth from a nutrient-poor environment. Cell proliferation studies undertaken under nutrient-limiting conditions have led us to define two distinct pathways by which tumor cells gain a competitive advantage over their nontransformed counterparts. One pathway is defined by enhanced capture of existing glucose and amino acids through nutrient-selective transporters. The key mediators of this pathway are AKT and its downstream effector, mTORC1. The other pathway depends on the uptake and degradation of extracellular proteins and lipids. Oncogenic forms of RAS are potent activators of this pathway. Many tumors appear capable of using both nutrient uptake pathways and can switch between them depending on extracellular nutrient conditions. Implications of these findings for tumor heterogeneity and therapeutic responsiveness will be discussed. Citation Format: Craig B. Thompson, Wilhelm Palm, Jiangbin Ye, Natalya N. Pavlova, Bryan King. Isogenic tumors can utilize heterogeneous mechanisms of nutrient uptake. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr PL02-01.