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).
Highlights
Tumor cells mainly obtain energy in a special metabolic condition, which is called the Warburg effect
The results showed that Phosphoglycerate k inase 1 (PGK1) promoted hepatocellular carcinoma (HCC) cell lines proliferation, and boosted metastasis via MYC-dependent PGK1 expression to modulate the HCC cells metabolism
The result indicated that SNU449 and HCCLM3 expressed higher levels of PGK1 protein compared to HL7702 cells
Summary
Tumor cells mainly obtain energy in a special metabolic condition, which is called the Warburg effect. PGK1 is a promoter of metastasis in colon cancer [8], which might be a potential protein biomarker of intracellular oxidative status in human colon carcinoma cells [9]. A recent article shows that acetylation at the K323 site of PGK1, as an important regulatory mechanism, promotes its enzymatic activity and cancer cell metabolism [16]. All of these findings indicate that PGK1 is a potential marker for progression in HCC. Proto-oncogene c-MYC as an upstream regulator links to the tumor-secreted protein PGK1 in the process of breast cancer development [22]. These results recommend a new view of PGK1 in HCC development
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