ArticleResearch (Washington, D.C.)2024
Integrating Single-Cell and Spatial Transcriptomics to Uncover and Elucidate GP73-Mediated Pro-Angiogenic Regulatory Networks in Hepatocellular Carcinoma.
Article in Research (Washington, D.C.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed.
- Targeting lactylation in hepatocellular carcinoma: Mechanistic insights and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
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- Crosstalk between lactylation and other post-translational modifications in health and diseases.Molecular biomedicine · 2026Review
- Lactylation-driven therapeutic resistance in cancer: Mechanisms and therapeutic opportunities.Genes & diseases · 2026Review
- Multidimensional nano-ion composite hydrogel based on enzymatic blood glucose control, gas therapy and ion liquid permeation for repairing diabetic wounds.Materials today. Bio · 2026Article
- Lactate metabolism and lactylation in cancer: from pathogenesis to therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Lactylation in Colorectal Cancer: Regulatory Networks, Functional Mechanisms, and Clinical Translational Potential.International journal of molecular sciences · 2026Review
- Advances in the mechanisms of extracellular vesicles and circulating tumor cells in hepatocellular carcinoma metastasis (Review).Molecular medicine reports · 2026Review
- Methyl-cantharidimide suppresses cyclin-dependent kinase 1 (CDK1) and induces oxeiptosis in liver cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Lactylation-related genes contribute to neurological injury and prognosis of acute ischemic stroke based on transcriptome and single-cell sequencing analysis.Cell & bioscience · 2026Article
- Protein Lactylation in Liver Disease: A Comprehensive Review.Expert reviews in molecular medicine · 2026Review
- Beyond a metabolite: lactate and lactylation in lung diseases.Respiratory research · 2026Review
- Mechanisms of lactylation modification in hepatocellular carcinoma treatment resistance.Gastroenterology report · 2026Review
- Integrated spatial and single-cell transcriptomics reveals RPL8 as a prognostic biomarker and therapeutic target in hepatocellular carcinoma.Translational oncology · 2026Article
- Lactate-lactylation in tumor angiogenesis and progression: mechanisms, biomarker potential, and therapeutic implications.Biomarker research · 2026Review
- Hypoxic Preconditioned Nanofat at 1% OCells · 2026Article
- Repurposed Acarbose Targets Nidogen-1 to Remodel the Tumor Stroma and Suppress Portal Vein Tumor Thrombus in Hepatocellular Carcinoma.Research (Washington, D.C.) · 2026Article
- Clonal evolution in gastrointestinal cancers: multi-omics insights into tumor heterogeneity, microenvironmental selection, and translational biomarkers.Frontiers in oncology · 2026Review
- Decoding the spatial logic of immune evasion in hepatocellular carcinoma: from single-cell profiling to spatial omics.Frontiers in immunology · 2026Review
- Single-cell RNA sequencing and spatial transcriptomic analysis reveal a distinct population of G6PDFrontiers in immunology · 2026Article
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Authors and funding
22 authors.
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Abstract
Hepatocellular carcinoma (HCC) was characterized as being hypervascular. In the present study, we generated a single-cell spatial transcriptomic landscape of the vasculogenic etiology of HCC and illustrated overexpressed Golgi phosphoprotein 73 (GP73) HCC cells exerting cellular communication with vascular endothelial cells with high pro-angiogenesis potential via multiple receptor-ligand interactions in the process of tumor vascular development. Specifically, we uncovered an interactive GP73-mediated regulatory network coordinated with c-Myc, lactate, Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway, and endoplasmic reticulum stress (ERS) signals in HCC cells and elucidated its pro-angiogenic roles in vitro and in vivo. Mechanistically, we found that GP73, the pivotal hub gene, was activated by histone lactylation and c-Myc, which stimulated the phosphorylation of downstream STAT3 by directly binding STAT3 and simultaneously enhancing glucose-regulated protein 78 (GRP78)-induced ERS. STAT3 potentiates GP73-mediated pro-angiogenic functions. Clinically, serum GP73 levels were positively correlated with HCC response to anti-angiogenic regimens and were essential for a prognostic nomogram showing good predictive performance for determining 6-month and 1-year survival in patients with HCC treated with anti-angiogenic therapy. Taken together, the aforementioned data characterized the pro-angiogenic roles and mechanisms of a GP73-mediated network and proved that GP73 is a crucial tumor angiogenesis niche gene with favorable anti-angiogenic potential in the treatment of HCC.
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