Dataset Information

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.

SUBMITTER: Gao F

PROVIDER: S-EPMC8138007 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Gao Feng F Zhang Xiaojun X Wang Shuyue S Zheng Lihua L Sun Ying Y Wang Guannan G Song Zhenbo Z Bao Yongli Y

Cell death & disease 20210520 6

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 ...[more]

PMID: 34016961

Similar Datasets

Project description:BackgroundAltered glycolysis is the most fundamental metabolic change associated with the Warburg effect. Some glycolytic enzymes such as PKM2, the dominant pyruvate kinase in cancer cells, have been shown to engage in non-glycolytic functions that contribute to tumor metabolism. However, the precise mechanisms are not completely understood.MethodsThe role of MNX1-AS1 in hepatocellular carcinoma progression was assessed both in vitro and in vivo. Northern blotting, RNA pulldown, mass spectrometry, RNA-binding protein immunoprecipitation, ChIP, luciferase reporter assays, RNA FISH and immunofluorescence staining were used to explore the detail molecular mechanism of MNX1-AS1 in hepatocellular carcinoma (HCC).ResultsHere we dissect how MNX1-AS1, a long non-coding RNA (lncRNA), reinforces the Warburg effect through facilitating the non-glycolytic actions of PKM2 in the cell nucleus. We found that MNX1-AS1 expression was frequently overexpressed in HCC-derived cell lines and tissues compared to their normal hepatic cell counterparts, a finding consistent with its status as pan-cancer expressed lncRNA. In the context of HCC, we show MNX1-AS1 acts as a scaffold to promote interactions between PKM2 and importin α5. In response to EGFR activation, the resulting ternary complex drives the translocation of PKM2 into the nucleus. In consequence, glycolytic pathway components including key mediators of the Warburg effect (LDHA, GLUT1 and PDK1) are upregulated though the coactivator function of PKM2. Manipulating MNX1-AS1 elicited robust effects on glycolysis associated with marked changes in HCC growth in vitro and in xenograft models, indicative of the significant contribution of MNX1-AS1 to tumorigenic phenotypes. Moreover, while MNX1-AS1 expression is driven by c-Myc, its actions associated with PKM2 were shown to be downstream and independent of c-Myc.ConclusionsGiven the status of MNX1-AS1 as a pan-cancer upregulated lncRNA, this implicitly highlights the potential of targeting MNX1-AS1 to selectively counter the Warburg effect in a range of tumor types.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets