TSP50 promotes the Warburg effect and hepatocyte proliferation via regulating PKM2 acetylation.

Abstract	Metabolic reprogramming is a hallmark of malignancy. Testes-specific protease 50 (TSP50), a newly identified oncogene, has been shown to play an important role in tumorigenesis. However, its role in tumor cell metabolism remains unclear. To investigate this issue, LC-MS/MS was employed to identify TSP50-binding proteins and pyruvate kinase M2 isoform (PKM2), a known key enzyme of aerobic glycolysis, was identified as a novel binding partner of TSP50. Further studies suggested that TSP50 promoted aerobic glycolysis in HCC cells by maintaining low pyruvate kinase activity of the PKM2. Mechanistically, TSP50 promoted the Warburg effect by increasing PKM2 K433 acetylation level and PKM2 acetylation site (K433R) mutation remarkably abrogated the TSP50-induced aerobic glycolysis, cell proliferation in vitro and tumor formation in vivo. Our findings indicate that TSP50-mediated low PKM2 pyruvate kinase activity is an important determinant for Warburg effect in HCC cells and provide a mechanistic link between TSP50 and tumor metabolism.
Authors	Feng Gao, Xiaojun Zhang, Shuyue Wang, Lihua Zheng, Ying Sun, Guannan Wang, Zhenbo Song, Yongli Bao
Journal	Cell death & disease (Cell Death Dis) Vol. 12 Issue 6 Pg. 517 (05 20 2021) ISSN: 2041-4889 [Electronic] England
PMID	34016961 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Biomarkers, Tumor Carrier Proteins Membrane Proteins Thyroid Hormones Serine Endopeptidases testis-specific protease 50
Topics	Acetylation Animals Biomarkers, Tumor Carcinoma, Hepatocellular (enzymology, metabolism, pathology) Carrier Proteins (metabolism) Cell Line, Tumor Cell Proliferation (physiology) Female HEK293 Cells Hepatocytes (cytology, enzymology, metabolism) Heterografts Humans Liver Neoplasms (enzymology, metabolism, pathology) Membrane Proteins (metabolism) Mice Mice, Inbred BALB C Mice, Nude Oncogenes Serine Endopeptidases (metabolism) Thyroid Hormones (metabolism) Transfection Warburg Effect, Oncologic Thyroid Hormone-Binding Proteins

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