PGK1 Drives Hepatocellular Carcinoma Metastasis by Enhancing Metabolic Process

Abstract

During the proliferation and metastasis, the tumor cells prefer glycolysis (Warburg effect), but its exact mechanism remains largely unknown. In this study, we demonstrated that phosphoglycerate kinase 1 (PGK1) is an important enzyme in the pathway of metabolic glycolysis. We observed a significant overexpression of PGK1 in hepatocellular carcinoma tissues, and a correlation between PGK1 expression and poor survival of hepatocellular carcinoma patients. Also, the depletion of PGK1 dramatically reduced cancer cell proliferation and metastasis, indicating an oncogenic role of PGK1 in liver cancer progression. Further experiments showed that PGK1 played an important role in MYC-induced metabolic reprogramming, which led to an enhanced Warburg effect. Our results revealed a new effect of PGK1, which can provide a new treatment strategy for hepatocellular carcinoma, as PGK1 is used to indicate the prognosis of hepatocellular carcinoma (HCC).

MicroRNA‐450b‐3p inhibits cell growth by targeting phosphoglycerate kinase 1 in hepatocellular carcinoma

“…To confirm this prediction, the relationship between miR‐450b‐3p and PGK1 expression was first examined in HCC cases. In this study, PGK1 mRNA and protein expression were significantly upregulated in HCC tumor tissues (Figure B‐E), which is consistent with previous reports . An inverse correlation between miR‐450b‐3p and PGK1 protein expression was observed using Pearson's correlation analysis, whereas there was no correlation between miR‐450b‐3p and PGK1 mRNA expression (Figure F,G).…”

“…PGK1, an important enzyme in metabolic glycolysis, has been considered as an oncogene in various human malignancies . PGK1 is upregulated in HCC and negatively correlated to poor survival in patients with HCC .…”

“…These results indicated that PGK1 is a direct target of miR‐450b‐3p in HCC. Notably, the inhibitory effect of miR‐450b‐3p on HCC proliferation could be abrogated by overexpression of PGK1 which has been reported to promote the tumorigenesis and development of HCC …”

“…PGK1, an important enzyme in metabolic glycolysis, has been considered as an oncogene in various human malignancies. 11,[15][16][17] PGK1 is upregulated in HCC and negatively correlated to poor survival in patients with HCC. 11,12 Consistently, we also observed significant overexpression of PGK1 mRNA and protein in HCC specimens.…”

Quantitative Global Proteome and Lysine Succinylome Analyses Reveal the Effects of Energy Metabolism in Renal Cell Carcinoma

“…Among the glycolytic enzymes, PGK1 catalyzes a crucial step of glycolysis, transferring a phosphate group from 1,3‐biphosphoglycerate to ADP and thereby forming ATP and 3‐phosphoglycerate . PGK1 is also believed to participate in tumorigenesis, autophagy, and cancer metastasis . As a predictor of poor survival and a prognostic biomarker of resistance to chemotherapeutics, PGK1 is overexpressed in many malignancies, including breast cancer, liver cancer, and gastric cancer .…”