ArticleOncogene2021
O-GlcNAc modified-TIP60/KAT5 is required for PCK1 deficiency-induced HCC metastasis.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 53 citations in OpenAlex.
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- Novel noscapine derivative induces AML differentiation by dual-engaging DHODH and mitochondrial lipids to trigger a metabolic-epigenetic-transcriptional cascade.Acta pharmaceutica Sinica. B · 2026Article
- Neu5Gc-associated Serum Immunoglobulin G Glycosylation as a Diagnostic Biomarker for Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2026Article
- Mechanism exploration of di(2-ethylhexyl) phthalate (DEHP)-induced hepatocellular carcinoma via network toxicology and molecular docking analysis.Discover oncology · 2026Article
- Low expression of OXCT1 promote colorectal cancer liver metastasis by upregulating CDK8 and β-catenin via H3 acetylation.Genes & diseases · 2026Article
- Construction and Multi-dimensional Validation of a Lactylation-Related Signature for Glioblastoma Multiforme Prognostic and Therapeutic Purposes.Molecular biotechnology · 2026Article
- Decoding the regulatory code: O-GlcNAcylation in epithelial-mesenchymal transition (EMT).The Journal of biological chemistry · 2026Review
- Development of a prognostic model for thyroid cancer based on mitochondrial metabolism-related genes and immune profiling.World journal of surgical oncology · 2026Article
- Post-Translational Modifications of Histones and Non-Histones in Liver Disease and Traditional Chinese Medicine Treatment: A Narrative Review.Pharmacogenomics and personalized medicine · 2026Review
- PCK1 attenuates intrahepatic cholangiocarcinoma progression by suppressing lactate accumulation and PI3K-AKT signaling.Functional & integrative genomics · 2025Article
- Protective effect of phosphoenolpyruvate carboxykinase 1 on inflammation and fibrotic progression of IgA nephropathy.Renal failure · 2025Article
- Molecular network of metabolic reprogramming and precision diagnosis and treatment of hepatocellular carcinoma.Biomarker research · 2025Review
- Acetylated KIAA1429 by TIP60 facilitates metastasis and immune evasion of hepatocellular carcinoma via N6-methyladenosine-KDM5B-mediated regulation of FoxO1.Cell death discovery · 2025Article
- Post-translational modifications of epigenetic modifier TIP60: their role in cellular functions and cancer.Epigenetics & chromatin · 2025Review
- O-GlcNAcylation of hexokinase 2 modulates mitochondrial dynamics and enhances the progression of lung cancer.Molecular and cellular biochemistry · 2025Article
- The role of acetylation and deacetylation in cancer metabolism.Clinical and translational medicine · 2025Review
- PCK1 as a target for cancer therapy: from metabolic reprogramming to immune microenvironment remodeling.Cell death discovery · 2024Review
- Constructing a disulfidptosis-related prognostic signature of hepatocellular carcinoma based on single-cell sequencing and weighted co-expression network analysis.Apoptosis : an international journal on programmed cell death · 2024Article
- FOXM1 Upregulates O-GlcNAcylation Level Via The Hexosamine Biosynthesis Pathway to Promote Angiogenesis in Hepatocellular Carcinoma.Cell biochemistry and biophysics · 2024Article
- Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant glucose metabolism and elevated O-linked β-N-acetylglucosamine modification (O-GlcNAcylation) are hallmarks of hepatocellular carcinoma (HCC). Loss of phosphoenolpyruvate carboxykinase 1 (PCK1), the major rate-limiting enzyme of hepatic gluconeogenesis, increases hexosamine biosynthetic pathway (HBP)-mediated protein O-GlcNAcylation in hepatoma cell and promotes cell growth and proliferation. However, whether PCK1 deficiency and hyper O-GlcNAcylation can induce HCC metastasis is largely unknown. Here, gain- and loss-of-function studies demonstrate that PCK1 suppresses HCC metastasis in vitro and in vivo. Specifically, lysine acetyltransferase 5 (KAT5), belonging to the MYST family of histone acetyltransferases (HAT), is highly modified by O-GlcNAcylation in PCK1 knockout hepatoma cells. Mechanistically, PCK1 depletion suppressed KAT5 ubiquitination by increasing its O-GlcNAcylation, thereby stabilizing KAT5. KAT5 O-GlcNAcylation epigenetically activates TWIST1 expression via histone H4 acetylation, and enhances MMP9 and MMP14 expression via c-Myc acetylation, thus promoting epithelial-mesenchymal transition (EMT) in HCC. In addition, targeting HBP-mediated O-GlcNAcylation of KAT5 inhibits lung metastasis of HCC in hepatospecific Pck1-deletion mice. Collectively, our findings demonstrate that PCK1 depletion increases O-GlcNAcylation of KAT5, epigenetically induces TWIST1 expression and promotes HCC metastasis, and link metabolic enzyme, post-translational modification (PTM) with epigenetic regulation.
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