The Role of Pyruvate Kinase M2 Posttranslational Modification in the Occurrence and Development of Hepatocellular Carcinoma

• Published in: Cell biochemistry and function 2024-09, Vol.42 (7), p.e4125-n/a
• Main Authors: Chunlian, Zhao, Qi, Wan, Rui, Zhao
• Format: Article
• Language: English
• Subjects: Animals; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Carrier Proteins - metabolism; glycolysis; hepatocellular carcinoma; Humans; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Membrane Proteins - metabolism; posttranslational modification; Protein Processing, Post-Translational; Pyruvate Kinase - metabolism; pyruvate kinase M2; Thyroid Hormone-Binding Proteins; Thyroid Hormones - metabolism; tumorigenesis and development
• ISSN: 0263-6484; 1099-0844; 1099-0844
• DOI: 10.1002/cbf.4125

ABSTRACT Hepatocellular carcinoma (HCC) is one of the deadly malignant tumors that directly leads to the death of nearly one million people worldwide every year, causing a serious burden on society. In the presence of sufficient oxygen, HCC cells rapidly generate energy through aerobic glycolysis, which promotes tumor cell proliferation, immune evasion, metastasis, angiogenesis, and drug resistance. Pyruvate kinase M2 (PKM2) is a key rate‐limiting enzyme in glycolysis. In recent years, studies have found that PKM2 not only exerts pyruvate kinase activity in the process of glucose metabolism, but also exerts protein kinase activity in non‐metabolic pathways to affect tumor cell processes, and its activity is flexibly regulated by various posttranslational modifications such as acetylation, phosphorylation, lactylation, ubiquitination, SUMOylation, and so forth. This review summarizes the role of posttranslational modifications of PKM2‐related sites in the development of HCC. Summary Hepatocellular carcinoma (HCC) is one of the deadly malignant tumors. Even in the case of sufficient oxygen, HCC cells rapidly generate energy through aerobic glycolysis. Pyruvate kinase M2 (PKM2) is a key rate‐limiting enzyme in glycolysis. Recent studies have found that the posttranslational modification of PKM2 flexibly regulates its pyruvate kinase activity and protein kinase activity, thus affecting the important physiological functions of cells. This review summarizes the role of posttranslational modifications of PKM2‐related sites in the development of HCC. It has been found that posttranslational modifications of PKM2‐related sites mostly promote the occurrence, metastasis and drug resistance of HCC, often suggesting poor prognosis.