title: TRIM35 Interacts with pyruvate kinase isoform M2 to suppress the Warburg effect and tumorigenicity in hepatocellular carcinoma.
abstract: Tripartite motif-containing protein 35 (TRIM35) is a member of RBCC family, which has a highly conserved order consisting of a RING domain followed by one or two B-Box domains and then a coiled-coil domain. We previously identified TRIM35 as a novel tumor suppressor in human hepatocellular carcinoma (HCC). However, the molecular mechanism that TRIM35 uses to suppress tumorigenicity is largely unknown. Pyruvate kinase isoform M2 (PKM2) has been demonstrated to have a central role in metabolic reprogramming during cancer progression. Phosphorylation of PKM2 tyrosine residue 105 (Y105) regulates PKM2 to provide a metabolic advantage to tumor cells, thereby promoting tumor growth. In the present work, mass spectrometry analysis demonstrated an interaction between TRIM35 and PKM2. Co-IP experiments confirmed that TRIM35 interacts with PKM2 and that the coiled-coil domain is required for such an interaction. Furthermore, the coiled-coil domain mediates decreases in the Warburg effect and in the cell proliferation of HCC cells. In addition, TRIM35 suppresses the tumorigenicity of HCC cells through the blockade of PKM2 Y105 phosphorylation. Collectively, our data reveal a new function for TRIM35, which is to regulate the Warburg effect and tumorigenicity through interaction with PKM2 in HCC.
authors.affiliation: 1] Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China [2] State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: W
authors.initials: W
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: F
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: D
authors.initials: D
authors.lastname: Jia
authors.affiliation: Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: M
authors.initials: M
authors.lastname: Yao
authors.affiliation: 1] Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China [2] State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: X
authors.identifier: 000000018872668X
authors.initials: X
authors.lastname: He
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D063646:Carcinogenesis / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006019:Glycolysis; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000502:physiology*; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D013963:Thyroid Hormones / Q000502:physiology*; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D008565:Membrane Proteins; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins; C476418:TRIM35 protein, human