Research News

Newly identified function and modification of PGK1 in liver cancer

Source: Time: 2016-10-31

A research team led by Dr. Daming Gao, at Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), recently characterized a new function and modification of PGK1, and elucidated their regulatory mechanism and uncovered their potential implications in liver cancer diagnose and treatment, which was just published online in Hepatology on Oct. 24th, 2016. This study is the fruit of a collaboration with Prof. Jun Qin (Institute of Health Sciences, SIBS, CAS), Prof. Huiyong Yin (the Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, SIBS, CAS), Prof. Hu Zhou (Shanghai Institute of Materia Medica, CAS), Prof. Dan Ye (Fudan University), and Prof. Qinghai Ye( Liver Cancer Institute & Zhongshan Hospital, Fudan University).

Under aerobic conditions, normal cells process glucose, first to pyruvate via glycolysis in the cytosol and thereafter to carbon dioxide in the mitochondria, while under anaerobic conditions, glycolysis is favored and relatively little pyruvate is dispatched to the oxygen-consuming mitochondria. However, cancer cells reprogram their glucose metabolism by limiting their energy metabolism largely to glycolysis, even in the presence of oxygen, termed “aerobic glycolysis”. Phosphoglycerate kinase 1 (PGK1), catalyzes the conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate and generates a molecule of ATP, plays an important role in metabolic glycolysis pathway.

Gao Lab mainly focuses their research on cancer signaling and metabolism regulation, especially the key post-translational modifications of important signaling transducers, which may reveal novel cancer-specific signaling axis and lead to identification of new therapeutic targets for cancer treatment. In this study, Hongli Hu et al., observed a significant over-expression of PGK1 in liver cancer tissues and a negative correlation between PGK1 expression and liver cancer patient survival. Furthermore, depletion of PGK1 dramatically reduced cancer cell proliferation and tumorigenesis, indicating an oncogenic role of PGK1 in liver cancer progression. Moreover, they identified one acetylation site (K323) of PGK1 as an important regulatory mechanism for promoting its enzymatic activity and cancer cell proliferation. And they further characterized P300/CBP associated factor (PCAF) and sirtuin 7 (SIRT7) as the enzymes regulating PGK1’s acetylation from both directions in liver cancer cells. Thus, these findings improved our current knowledge of oncogenic function of PGK1 in liver cancer and provided a potential therapeutic strategy for drug design aiming at metabolic enzymes.

This work was supported by the grants from the Ministry of Science and Technology of China and the National Natural Science Foundation of China.

AUTHOR CONTACT:
Gao Daming, Ph.D.
Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
Tel: +86-21-54921281;
E-mail: dgao@sibcb.ac.cn


Legend: Graphic model of K323 acetylation dependent regulation of PGK1 function in liver cancer. K323 acetylation enhanced PGK1 enzymatic activity and promoted the efficiency of glycolytic metabolism, which resulted in liver cancer cell proliferation and tumorigenesis. K323 acetylation was positively regulated by PCAF and negatively modulated by SIRT7, indicating a bi-directional control of PGK1 function. (Image provided by Prof. Gao Daming’s lab)

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