Abstract 3542: Coordination of glutamine and glucose metabolism in pancreatic cancer

Abstract

Abstract Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer related deaths in the United States. Due to early metastasis by the time it is diagnosed it advances to advanced stages and becomes unresectable. Oncogene mediated metabolic reprogramming has been shown to promote the growth, maintenance and metastasis of tumors in pancreatic ductal adenocarcinoma. Pancreatic tumors route majority of glucose and glutamine for biomass generation and maintenance of redox potential. The aim of this study was to investigate the link between glutamine and glucose metabolism in pancreatic cancer cells. We primarily focused on the role of glutamine mediated regulation of glucose metabolism. We observed that glutamine deprivation reduces pancreatic cancer cell growth as suggested by the previous studies. We further investigated how pancreatic cancer cells adapt to glutamine deprived conditions. We observed that glucose uptake increases significantly upon glutamine deprivation. However, GLUT1 expression showed a contrasting decreased expression under conditions of glutamine deprivation. Using tandem mass spectrometry based metabolomic analysis we observed that glutamine deprivation does not alter glycolysis. However, the TCA cycle, amino acid metabolism and glutathione metabolism were significantly impacted in glutamine deprived cells. We noticed a significant increase in the levels of hydroxyglutarate and succinyl CoA levels in the TCA cycle. These changes were accompanied with an increase in GSH to GSSG ratio that reflects a possibility for alternative pathways involved in redox maintenance under glutamine deprived conditions. Hence, we conclude that glutamine metabolism significantly impacts the uptake and metabolism of glucose in pancreatic cancer cells. Citation Format: Enza Vernucci, Venugopal Gunda, Surendra Shukla, Pankaj K. Singh. Coordination of glutamine and glucose metabolism in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3542. doi:10.1158/1538-7445.AM2017-3542