ArticleMolecular cancer2024
ESM1 enhances fatty acid synthesis and vascular mimicry in ovarian cancer by utilizing the PKM2-dependent warburg effect within the hypoxic tumor microenvironment.
Article in Molecular cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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73 citing papers in PubMed.
- Subtype-specific mechanisms of lipid metabolism in gynecological malignancies and novel targeted intervention strategies (Review).Oncology letters · 2026Review
- T cell-derived CCL5 drives macrophage immunometabolic remodeling in chronic prostatitis via the CCR5-ERK-PKM2/HIF-1α axis.Redox biology · 2026Article
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- OTUB1 Promotes HCC Progression by Regulating Glycolysis Through Deubiquitination of PKM2.Molecular carcinogenesis · 2026Article
- Reshaping psoriasis topical therapy: Continuous hydrogenation orchestrates 'redox-metabolic homeostasis' for efficient remission and relapse intervention.Bioactive materials · 2026Article
- Rewiring cancer cell fate toward vasculogenic mimicry: from classical to unconventional processes.Cancer metastasis reviews · 2026Review
- PRRC2A-mediated mCell death & disease · 2026Article
- Single-cell and spatial transcriptomics map lung-adaptive metastasis programs through Exoc4, Cd36-vasculogenic mimicry, and Cxcr2 signaling in triple-negative breast cancer.Cell death & disease · 2026Article
- SAP18 drives vasculogenic mimicry in esophageal squamous cell carcinoma: a machine learning and multi-omics investigation.NPJ precision oncology · 2026Article
- UBA2: the gatekeeper of the sumoylation pathway and its multifaceted roles in human diseases and therapeutic prospects.Clinical and experimental medicine · 2026Review
- ESM1 drives cisplatin resistance and ferroptosis resistance via ERBB2/FAK/SRC/HSPB1/NF-κB signaling in ovarian cancer.iScience · 2026Article
- Sulconazole Suppresses Colorectal Cancer Immune Evasion by Inhibiting Glycolysis to Upregulate OVOL2 PARylation and Induce PANoptosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Targeting Pyruvate Kinase M2: Signal Transduction Pathways and Exploration of Cancer Therapeutic Strategies.The AAPS journal · 2026Review
- PKM2 Lactylation Promotes Colorectal Cancer Vasculogenic Mimicry and Bevacizumab Resistance by Facilitating FOSL1 Super-enhancer Formation.Cancer research · 2026Article
- Fatty Acid Metabolism in Health and Cancer: From Fundamental Mechanisms to Therapeutic Application.MedComm · 2026Review
- ESM1 drives cancer angiogenesis and bevacizumab resistance via trioleate synthesis.Neoplasia (New York, N.Y.) · 2026Article
- Nuclear hexokinase 2 couples hyperglycemia to MYC-driven glycolytic and stemness programs in bladder cancer.Cell death & disease · 2026Article
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- Dissecting the aberrant vasculature of glioblastoma: mechanisms and therapeutic targets.Cancer metastasis reviews · 2026Review
- Exosomal microRNA-448 suppresses the malignant behaviors of liver cancer cells by targeting RAB7A and inhibiting glycolysis.Oncology letters · 2026Article
13 more citing papers are in PubMed but not listed here.
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Abstract
backgroundThe hypoxic tumor microenvironment is a key factor that promotes metabolic reprogramming and vascular mimicry (VM) in ovarian cancer (OC) patients. ESM1, a secreted protein, plays an important role in promoting proliferation and angiogenesis in OC. However, the role of ESM1 in metabolic reprogramming and VM in the hypoxic microenvironment in OC patients has not been determined.
methodsLiquid chromatography coupled with tandem MS was used to analyze CAOV3 and OV90 cells. Interactions between ESM1, PKM2, UBA2, and SUMO1 were detected by GST pull-down, Co-IP, and molecular docking. The effects of the ESM1-PKM2 axis on cell glucose metabolism were analyzed based on an ECAR experiment. The biological effects of the signaling axis on OC cells were detected by tubule formation, transwell assay, RT‒PCR, Western blot, immunofluorescence, and in vivo xenograft tumor experiments.
resultsOur findings demonstrated that hypoxia induces the upregulation of ESM1 expression through the transcription of HIF-1α. ESM1 serves as a crucial mediator of the interaction between PKM2 and UBA2, facilitating the SUMOylation of PKM2 and the subsequent formation of PKM2 dimers. This process promotes the Warburg effect and facilitates the nuclear translocation of PKM2, ultimately leading to the phosphorylation of STAT3. These molecular events contribute to the promotion of ovarian cancer glycolysis and vasculogenic mimicry. Furthermore, our study revealed that Shikonin effectively inhibits the molecular interaction between ESM1 and PKM2, consequently preventing the formation of PKM2 dimers and thereby inhibiting ovarian cancer glycolysis, fatty acid synthesis and vasculogenic mimicry.
conclusionOur findings demonstrated that hypoxia increases ESM1 expression through the transcriptional regulation of HIF-1α to induce dimerization via PKM2 SUMOylation, which promotes the OC Warburg effect and VM.
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