Monitoring the Switch: The Warburg Effect and Targeted Proteomic Analysis of Cancer Metabolism

J.      Patrick Murphy; Patrice      D. Cote; Devanand      M. Pinto

Abstract

Cancer cells dramatically alter their metabolism in order to increase the production rate of intermediates required for nucleic and fatty acid biosynthesis in rapidly proliferating cells. While not well understood, dysregulation of oncogenes and tumour suppressors appears to result in the altered expression of specific isoforms of glycolysis proteins. A full understanding of glycolytic alterations in cancer through a systems biology approach requires tools to observe changes in the set of proteins that make up the glycolytic proteome. We propose that a targeted proteomics approach employing multiple reaction monitoring (MRM) is an excellent strategy to quantitatively monitor sets of proteins, such as those making up the glycolytic proteome. MRM is particularly well suited to proteins of glycolysis as they are of moderate to high abundance. Such systems-based efforts provide a means to understand the mechanisms for an altered glycolytic proteome in cancer, perhaps leading to novel drug targets and metabolic signatures for use in cancer prognosis.

Keywords: Cancer, glycolysis, MRM, targeted proteomics, warburg effect, metabolism, nucleic, fatty acid biosynthesis, dysregulation, renal cell carcinomas, Pyruvate Kinase M2, Hexokinase 2 (HK2)