ArticleOncogene2022
ISCA2 inhibition decreases HIF and induces ferroptosis in clear cell renal carcinoma.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 56 citations in OpenAlex.
- Ferroptosis and tumor microenvironment: orchestrating therapy resistance, immune evasion, and metastatic events.Medical oncology (Northwood, London, England) · 2026Review
- Role ofJournal of fungi (Basel, Switzerland) · 2026Article
- The iron-sulfur cluster assembly factor FDX2 is required for tumor initiation but not for growth of established tumors in transplantation models.The Journal of biological chemistry · 2026Article
- MT1G promotes the progression of ccRCC by suppressing ferroptosis through activation of the PI3K-AKT pathway.Translational oncology · 2026Article
- A multi-programmed cell death-related LncRNA signature for prognosis and immune microenvironment evaluation in kidney renal clear cell carcinoma.Scientific reports · 2026Article
- MTF1 attenuates ferroptosis and cuproptosis synergistic potentiation in gastric cancer.Cell death and differentiation · 2026Article
- Regulatory networks of iron sulfur cluster biology in cancer mechanisms and therapeutic perspectives.iScience · 2026Review
- Ferroptosis in renal cell carcinoma: integrative multi-omics insights and therapeutic perspectives.International journal of surgery (London, England) · 2026Article
- The role of ferroptosis in renal cell carcinoma: molecular mechanisms and therapeutic implications.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Beyond angiogenesis: integrating ferroptosis and metabolic rewiring for next-generation RCC therapy.Frontiers in oncology · 2026Review
- Fueling Death: The Metabolic Control of Ferroptosis.Advances in experimental medicine and biology · 2026Review
- Smart Colloidal Systems as Drug Delivery and Therapeutic Modulation Platforms for Renal Cell Carcinoma.International journal of nanomedicine · 2026Review
- Formononetin alleviated cisplatin-induced acute kidney injury by orchestrating renal tubular cell ferroptosis via PI3K/AKT/NRF2 pathway.Frontiers in pharmacology · 2026Article
- Ferroptosis and cuproptosis in head and neck squamous cell carcinoma: interconnected mechanisms and therapeutic implications.Frontiers in pharmacology · 2026Review
- Exploring Natural Products to Target Ferroptosis in Urologic Malignancies: Advancements from Molecular Mechanisms to Therapeutic Strategies.Chinese journal of integrative medicine · 2025Review
- Ferroptosis in Cancer and Inflammatory Diseases: Mechanisms and Therapeutic Implications.MedComm · 2025Review
- The HIF axes in cancer: angiogenesis, metabolism, and immune-modulation.Trends in biochemical sciences · 2025Review
- Multi-Omic Insight Into the Molecular Networks of Mitochondrial Dysfunction in the Pathogenesis of Primary Open-Angle Glaucoma.Translational vision science & technology · 2025Article
- Increased ZNF83 is a potential prognostic biomarker and regulates oxidative stress-induced ferroptosis in clear cell renal cell carcinoma.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Disulfidptosis, a novel regulated cell death to predict survival and therapeutic response in kidney renal clear cell carcinoma.Discover oncology · 2025Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, is typically initiated by inactivation of the von Hippel Lindau (VHL) gene, which results in the constitutive activation of the hypoxia inducible factors, HIF-1α and HIF-2α. Using a high throughput screen, we identify novel compounds that decrease HIF-1/2α levels and induce ferroptosis by targeting Iron Sulfur Cluster Assembly 2 (ISCA2), a component of the late mitochondrial Iron Sulfur Cluster (L-ISC) assembly complex. ISCA2 inhibition either pharmacologically or using siRNA decreases HIF-2α protein levels by blocking iron-responsive element (IRE)-dependent translation, and at higher concentrations, also decreases HIF-1α translation through unknown mechanisms. Additionally, ISCA2 inhibition triggers the iron starvation response, resulting in iron/metals overload and death via ferroptosis. ISCA2 levels are decreased in ccRCC compared to normal kidney, and decreased ISCA2 levels are associated with pVHL loss and with sensitivity to ferroptosis induced by ISCA2 inhibition. Strikingly, pharmacological inhibition of ISCA2 using an orally available ISCA2 inhibitor significantly reduced ccRCC xenograft growth in vivo, decreased HIF-α levels and increased lipid peroxidation, suggesting increased ferroptosis in vivo. Thus, the targeting of ISCA2 may be a promising therapeutic strategy to inhibit HIF-1/2α and to induce ferroptosis in pVHL deficient cells.
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