GTPBP4 promotes hepatocellular carcinoma progression and metastasis via the PKM2 dependent glucose metabolism

Zhou, Qiang; Yin, Yuehui; Yu, Ming; Gao, Dongmei; Sun, Jialei; Yang, Zhixu; Weng, Juyang; Chen, Wanyong; Atyah, Manar; Shen, Ying‐Hao; Ye, Qing–Hai; Li, Chia-Wei; Hung, Mien‐Chie; Dong, Qiongzhu; Zhou, Chixing; Ren, Ning

doi:10.1016/j.redox.2022.102458

Cited by 46 publications

(32 citation statements)

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“…It has been reported that Guanosine triphosphate binding protein 4 (GTPBP4) is associated with poor prognosis in HCC patients ( 59 ). Additional reports have explored the role of GTPBP4 in metabolic regulation and the potential mechanisms involved in HCC development and metastasis ( 60 ). GTPBP4 induces the dimer conformation of PKM2 through the SUMOylation to promote the aerobic glycolysis of HCC, thus promoting the progression and metastasis of HCC ( 61 ).…”

Section: Discussionmentioning

confidence: 99%

Single-cell transcriptome analysis reveals the metabolic changes and the prognostic value of malignant hepatocyte subpopulations and predict new therapeutic agents for hepatocellular carcinoma

et al. 2023

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BackgroundThe development of HCC is often associated with extensive metabolic disturbances. Single cell RNA sequencing (scRNA-seq) provides a better understanding of cellular behavior in the context of complex tumor microenvironments by analyzing individual cell populations. MethodsThe Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data was employed to investigate the metabolic pathways in HCC. Principal component analysis (PCA) and uniform manifold approximation and projection (UMAP) analysis were applied to identify six cell subpopulations, namely, T/NK cells, hepatocytes, macrophages, endothelial cells, fibroblasts, and B cells. The gene set enrichment analysis (GSEA) was performed to explore the existence of pathway heterogeneity across different cell subpopulations. Univariate Cox analysis was used to screen genes differentially related to The Overall Survival in TCGA-LIHC patients based on scRNA-seq and bulk RNA-seq datasets, and LASSO analysis was used to select significant predictors for incorporation into multivariate Cox regression. Connectivity Map (CMap) was applied to analysis drug sensitivity of risk models and targeting of potential compounds in high risk groups.ResultsAnalysis of TCGA-LIHC survival data revealed the molecular markers associated with HCC prognosis, including MARCKSL1, SPP1, BSG, CCT3, LAGE3, KPNA2, SF3B4, GTPBP4, PON1, CFHR3, and CYP2C9. The RNA expression of 11 prognosis-related differentially expressed genes (DEGs) in normal human hepatocyte cell line MIHA and HCC cell lines HCC-LM3 and HepG2 were compared by qPCR. Higher KPNA2, LAGE3, SF3B4, CCT3 and GTPBP4 protein expression and lower CYP2C9 and PON1 protein expression in HCC tissues from Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas (HPA) databases. The results of target compound screening of risk model showed that mercaptopurine is a potential anti-HCC drug.ConclusionThe prognostic genes associated with glucose and lipid metabolic changes in a hepatocyte subpopulation and comparison of liver malignancy cells to normal liver cells may provide insight into the metabolic characteristics of HCC and the potential prognostic biomarkers of tumor-related genes and contribute to developing new treatment strategies for individuals.

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Section: Discussionmentioning

confidence: 99%

Single-cell transcriptome analysis reveals the metabolic changes and the prognostic value of malignant hepatocyte subpopulations and predict new therapeutic agents for hepatocellular carcinoma

et al. 2023

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“…[23][24][25] The SUMO pathway can induce cell proliferation, apoptosis resistance, and metastasis by regulating proteins involved in carcinogenesis. [26][27][28][29] Elevated expression of SUMO2/3 correlates with increased histological grade and the decreased overall survival of chondrosarcoma patients. 30 PML in COAD is hypo-SUMOylated due to the overaccumulation of SENP3 31 and the CRC transcriptional regulator p68 is modified by SUMO2 in CRC.…”

Section: Discussionmentioning

confidence: 99%

“…Existing studies have hinted at the important role of SUMOylation in human tumorigenesis 23–25 . The SUMO pathway can induce cell proliferation, apoptosis resistance, and metastasis by regulating proteins involved in carcinogenesis 26–29 . Elevated expression of SUMO2/3 correlates with increased histological grade and the decreased overall survival of chondrosarcoma patients 30 .…”

Section: Discussionmentioning

confidence: 99%

SUMO2/3 promotes the progression and oxaliplatin resistance of colorectal cancer through facilitating the SUMOylation at Ku80‐K307

Feng

Yuan

et al. 2023

BioFactors

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Colorectal cancer (CRC) is one of the most prevalent cancers worldwide and is typically treated with the FOLFOX regimen (folinic acid, 5‐fluorouracil, and oxaliplatin). However, oxaliplatin resistance remains a serious clinical problem. In the present study, we found that SUMO2/3 was overexpressed in CRC tissues and exogenous overexpression of SUMO2/3 promoted CRC cell proliferation, extension, and invasion and positively regulated the cell cycle. In contrast, SUMO2/3 gene knockdowns inhibited migration and repressed cell viability in vitro and in vivo. In addition, we found that SUMO2/3 was recruited to the cell nucleus and suppressed oxaliplatin‐induced apoptosis of CRC cells. Moreover, Ku80, a DNA‐binding protein essential for the repair of DNA double‐strand breaks, was confirmed to bind with SUMO2/3. Notably, Ku80 undergoes SUMOylation at K307 by SUMO2/3 and this correlated with apoptosis in CRC cells suffering oxaliplatin stress. Collectively, we found that SUMO2/3 plays a specific role in CRC tumorigenesis and acts through Ku80 SUMOylation which is linked with the development of CRC‐oxaliplatin resistance.

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“…The tumor necrosis factor alpha-induced protein 8 (TNFAIP8, TIPE) family is composed of four members: TIPE, TIPE1, TIPE2, and TIPE3 (Yang et al, 2022). Accumulating evidence suggests that TIPE is strongly associated with the development of various cancers by affecting cell proliferation, apoptosis, invasion, and metastasis (Goldsmith et al, 2017;Niture et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

TIPE drives a cancer stem-like phenotype by promoting glycolysis via PKM2/HIF-1α axis in melanoma

Tian,

Yang,

Zhao

et al. 2023

Preprint

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TIPE (TNFAIP8) has been identified as an oncogene and participates in tumor biology. However, how its role in the metabolism of tumor cells during melanoma development remains unclear. Here, we demonstrated that TIPE promoted glycolysis by interacting with pyruvate kinase M2 (PKM2) in melanoma. We found that TIPE induced PKM2 dimerization, thereby facilitating its translocation from the cytoplasm to the nucleus. TIPE-mediated PKM2 dimerization consequently promoted HIF-1α activation and glycolysis, which contributed to melanoma progression and increased its stemness features. Notably, TIPE specifically phosphorylated PKM2 at Ser 37 in an ERK-dependent manner. Consistently, the expression of TIPE was positively correlated with the levels of PKM2 Ser37 phosphorylation and cancer stem cell markers in melanoma tissues from clinical samples and tumor bearing mice. In summary, our findings indicate that the TIPE/PKM2/HIF-1α signaling pathway plays a pivotal role in promoting cancer stem cell properties by facilitating the glycolysis, which would provide a promising therapeutic target for melanoma intervention.

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GTPBP4 promotes hepatocellular carcinoma progression and metastasis via the PKM2 dependent glucose metabolism

Cited by 46 publications

References 50 publications

Single-cell transcriptome analysis reveals the metabolic changes and the prognostic value of malignant hepatocyte subpopulations and predict new therapeutic agents for hepatocellular carcinoma

Single-cell transcriptome analysis reveals the metabolic changes and the prognostic value of malignant hepatocyte subpopulations and predict new therapeutic agents for hepatocellular carcinoma

SUMO2/3 promotes the progression and oxaliplatin resistance of colorectal cancer through facilitating the SUMOylation at Ku80‐K307

TIPE drives a cancer stem-like phenotype by promoting glycolysis via PKM2/HIF-1α axis in melanoma

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