ArticleOncogene2022
iASPP is essential for HIF-1α stabilization to promote angiogenesis and glycolysis via attenuating VHL-mediated protein degradation.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Homeobox B13 activates the hypoxia-inducible factor 1 pathway through histone lactylation thereby reprogramming lipid metabolism and promoting sorafenib resistance in hepatocellular carcinoma.Journal of cell communication and signaling · 2026Article
- Inhibition of gastric adenocarcinoma proliferation by WSGC@MS: Role of KEAP1/NRF2 signaling pathway and autophagy regulation.Materials today. Bio · 2025Article
- Inhibitors of p53 Apoptosis-Stimulating Protein Mitigate Acute Kidney Injury by Modulating the HIF-1α/SLC7A11 Pathway to Suppress Ferroptosis.Journal of cellular and molecular medicine · 2025Article
- Ocular manifestations in pediatric tumor suppressor gene mutations: a case series and literature review of RB1, NF1, NF2, VHL, and TSC.BMC pediatrics · 2025Review
- PPP1R13L drives cervical cancer progression by suppressing p63-mediated PTEN transcription.Cellular and molecular life sciences : CMLS · 2025Article
- UBE2V1 Promotes Hepatocellular Carcinoma Progression by Forming a Positive Feedback Loop with HIF-1α.Research (Washington, D.C.) · 2025Article
- EIF4A3-Induced CircDHTKD1 regulates glycolysis in non-small cell lung cancer via stabilizing PFKL.Journal of cellular and molecular medicine · 2024Article
- Inhibitor of apoptosis stimulating protein of p53 protects against MPPMetabolic brain disease · 2024Article
- Enhancing intraneural revascularization following peripheral nerve injury through hypoxic Schwann-cell-derived exosomes: an insight into endothelial glycolysis.Journal of nanobiotechnology · 2024Article
- Targeting Cancer Metabolism to Improve Outcomes with Immune Checkpoint Inhibitors.Journal of immunotherapy and precision oncology · 2023Review
- The hypoxia-driven crosstalk between tumor and tumor-associated macrophages: mechanisms and clinical treatment strategies.Molecular cancer · 2022Review
- The function and regulatory mechanism of RNA-binding proteins in breast cancer and their future clinical treatment prospects.Frontiers in oncology · 2022Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia-inducible factor-1α (HIF-1α) plays central roles in the hypoxia response. It is highly expressed in multiple cancers, but not always correlated with hypoxia. Mutation of the von Hippel-Lindau (VHL) gene, which encodes an E3 ligase, contributes to the constructive activation of HIF-1α in specific tumor types, as exemplified by renal cell carcinoma; but how VHL wild-type tumors acquire this ability is not completely understood. Here, we found that the oncogene iASPP (inhibitor of apoptosis-simulating protein of p53) plays essential roles in such a context. Genetic inhibition of iASPP reduced tumor growth, accompanied by impaired angiogenesis, increased areas of tumor necrosis, and reduced glycolysis that was HIF-1α-dependent. These abilities of iASPP were validated by in vitro assays. Mechanistically, iASPP directly binds VHL at its β domain, a region also involved in HIF-1α binding, therefore blocking VHL's binding and the subsequent degradation of HIF-1α protein under normoxia. iASPP levels correlate with HIF-1α protein and vascular endothelial growth factor (VEGF) and the glucose transporter protein type 1(GLUT1), representative HIF-1α target genes, in human colon cancer tissues. Furthermore, inhibition of iASPP expression synergizes with low toxic dose of the HIF-1α inhibitor YC-1 to inhibit HIF-1α expression and tumor growth. Our findings suggest that iASPP contributes to HIF-1α activation in cancers, and that iASPP-mediated HIF-1α stabilization has potential as a therapeutic approach against cancer.
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