An Oncogenic Virus Promotes Cell Survival and Cellular Transformation by Suppressing Glycolysis

Zhu, Y., S. Ramos da Silva, M. He, Q. Liang, C. Lu, P. Feng, J. U. Jung and Gao, S. J. (2016). PLoS Pathogens, 12(5), e1005648. doi:10.1371/journal.ppat.1005648

Speaker: Ruei-Yi Chen (陳瑞怡)                          Time:14:00~15:00 Oct. 26, 2016

Commentator: Dr. Ai-Li Shiau (蕭璦莉老師)      Place: Room 601

Abstract:

Aerobic glycolysis, known as Warburg effect, is a hallmark of cancer. Aerobic glycolysis converts most of glucose to lactate regardless of the availability of oxygen and provides fast ATP production for cancer cells proliferation [1]. Kaposi’s sarcoma-associated herpesvirus (KSHV, HHV-8) is a human oncogenic virus. During latent infection, KSHV expresses only a few of viral genes including vFLIP (ORF71), vCyclin (ORF72), LANA (ORF73) and 12 precursor microRNAs (pre-miRNAs), which affect cell survival and proliferation [2]. Previous studies showed that KSHV infection could induce aerobic glycolysis in human endothelial cells (ECs) or primary effusion lymphoma (PEL) cells. However, these studies did not see cellular transformation by KSHV. Here, the authors found that in KSHV-transformed cells, aerobic glycolysis and oxidative phosphorylation were suppressed to support the survival and transformation of host cells. The authors reveal that KSHV-encoded vFLIP and the miRNA cluster downregulate glucose transporters GLUT1 and GLUT3 to reduce aerobic glycolysis thought activation the Akt-NF-κB signaling pathways. Consistently, overexpression of GLUT1 and GLUT3 promoted aerobic glycolysis, but impaired the Akt-NF-κB signaling pathways. Similar phenomena were observed in KSHV-infected KS tumors and PEL cells. In conclusion, the authors developed a model system of KSHV-induced malignant cellular transformation, and demonstrate that KSHV regulates aerobic glycolysis to adapt to nutrient stress within a tumor microenvironment for cancer cell proliferation and transformation.

References:

1.     Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009). Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science, 324(5930), 1029-1033. doi:10.1126/science.1160809

2.     Purushothaman, P., Uppal, T., Sarkar, R., & Verma, S. C. (2016). KSHV-Mediated Angiogenesis in Tumor Progression. Viruses, 8(7). doi:10.3390/v8070198