Abstract LB-25: CD147 promotes reprogramming of glucose metabolism and cell proliferation in HCC cells by inhibiting p53-dependent signaling pathway

Abstract

Abstract Background & Aims: Cancer cells exhibit the reprogrammed metabolism characterized by high level of glycolysis even in the presence of oxygen. Aerobic glycolysis, known as the Warburg effect, supplys cancer cells with the substrates required for biomass generation. To date, several intracellular signaling mediators have been identified in metabolic regulation of cancer cells. However, it remains largely ambiguous how molecules on cell surface are involved in regulation of cancer metabolism. Methods: In the current study, we established several HCC cell lines differing in their CD147 (a typical transmembrane glycoprotein) expression status by zinc-finger nuclease and RNAi techniques. Then, we systematically investigated the role of CD147 in the regulation of Warburg effect in HCC cells and explored the underlying mechanism. Results: We found that CD147 significantly contributed to the reprogramming of glucose metabolism in HCC cells through a p53-dependent way. CD147 facilitated the cell surface expression of MCT1 and lactate export, which led to the activation of PI3K/Akt/MDM2 pathway and thus increased p53 degradation. The gain/loss-of-function studies demonstrated that while CD147 promoted glycolysis mediated by p53-dependent up-regulation of GLUT1 and activation of PFKL; it inhibited mitochondrial biogenesis and functions mediated by p53-dependent down-regulation of PGC1α, TFAM and P53R2. Additionally, proliferation of HCC cells was suppressed by blocking CD147 and/or MCT1 which resulted in down-regulation of glucose metabolism. Conclusions: we demonstrate that CD147 is a crucial regulator of glucose metabolism. Citation Format: Qichao Huang, Jibin Li, Jinliang Xing. CD147 promotes reprogramming of glucose metabolism and cell proliferation in HCC cells by inhibiting p53-dependent signaling pathway. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-25. doi:10.1158/1538-7445.AM2014-LB-25