Pyruvate Kinase Isoform M2 Influences Autophagy and Related Processes in Hepatocellular Carcinoma Cells

Hepatocellular carcinoma (HCC) is the most common form of liver cancer that affects ~14 million people in the world. Like all cancers, HCC is a disease that arises from unstinted cellular growth initiated by genetic alterations, metabolic changes, and dysregulation in key cellular pathways. Of interest is the relationship between metabolism and cell proliferation/degradation for therapeutic targeting. Pyruvate kinase M2 is a dimeric, glycolytically inactive isoform of the final enzyme involved in glycolysis, that is often upregulated in cancerous tissue. It is thought that the enzymatic function of PKM2 outside of glycolysis contributes to the biosynthesis of anabolic intermediates used in cell growth and division. Autophagy is a recycling process by which cells selectively degrade defective components and is implicated in cell death pathways. Because PKM2 is upregulated in HCC and links metabolism and tumorigenesis, we investigate its role in regulating autophagy and associated processes. In this study, shRNA constructs were used to knockdown and overexpress the PKM2 isoform in vitro to observe its effect on autophagy and related processes, thus establishing a working model for how autophagy is regulated in HCC cells and potential therapeutic targeting