Fig. 8.

PKM2 inhibitor suppresses HCC cells progression in vivo (A) Orthotopic xenograft models were derived from PLC/PRF/5 Vector and PLC/PRF/5-GTPBP4 cells treated as indicated (left). Tumor volumes are shown (right). n = 6, one-way ANOVA. (B) Glucose metabolism of HCC in each group in (A) was confirmed by representative [¹⁸F]-PET-CT images at the end of therapy (4 weeks). (C) Orthotopic xenograft models were derived from HCCLM3 Control and HCCLM3-shGTPBP4 cells treated as indicated (left). Tumor volumes are shown (right). n = 6, one-way ANOVA. (D) Glucose metabolism of HCC in each group was confirmed by representative [¹⁸F]-PET-CT images at the end of therapy (4 weeks). n = 6, one-way ANOVA. (E) Representative images of H&E staining of lung tissues (left) and the number of lung metastatic foci (right) from each group shown in (A). n = 6, one-way ANOVA. (F) Representative images of H&E staining of lung tissues (upper) and the number of lung metastatic foci (lower) from each group shown in (B). n = 6, one-way ANOVA. (G) Schematic diagram illustrating role of GTPBP4 in promoting hepatocellular carcinoma progression. DNA methyltransferase, DNMT3A, negatively regulates GTPBP4 expression through GTPBP4 DNA promoter methylation modification. Active GTPBP4 (GTP bound) facilitates SUMO1 protein activation by UBA2, and acts as a linker bridging activated SUMO1 protein and PKM2 protein to induce PKM2 sumoylation to promote aerobic glycolysis in HCC. Furthermore, SUMO-modified PKM2 relocates from the cytoplasm to the nucleus and activates STAT3 signaling pathway and epithelial-mesenchymal transition (EMT). Together, the two ways contribute to the development of HCC. Abbreviations: IHC: immunohistochemical. *P < 0.05, **P < 0.01, ***P < 0.001.