ArticleProceedings of the National Academy of Sciences of the United States of America2022
Hypersensitivity to ferroptosis in chromophobe RCC is mediated by a glutathione metabolic dependency and cystine import via solute carrier family 7 member 11.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- From Gene to Enzyme: Multidimensional Decoding of the GGT Molecular Family and Its Clinical Tumor Diagnosis.Cancer medicine · 2025Pooled it
- Exploring regulated cell death in renal cell carcinoma: mechanistic insights and therapeutic perspectives.Apoptosis : an international journal on programmed cell death · 2026Review
- mTORC1 activation induces B7-H3-dependent metabolic reprogramming in renal cell carcinoma (RCC).Oncogene · 2026Article
- Reviving cancer vaccines in renal cell carcinoma: a new chapter in immunotherapy for kidney cancer.Immuno-oncology technology · 2026Review
- Profilin-1 Promotes Chromophobe Renal Cell Carcinoma Malignancy.bioRxiv : the preprint server for biology · 2026Article
- Article
- Gut microbiota induces dysspermatogenesis via microbial-derived phenylacetylglycine in Ggt1-deficient mice.Microbiome · 2026Article
- Ferroptosis as a therapeutic vulnerability in ARID1A-deficient bladder cancer.Communications biology · 2026Article
- Dual role of lactate in ferroptosis: Mechanisms, pathophysiology and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
- Beyond angiogenesis: integrating ferroptosis and metabolic rewiring for next-generation RCC therapy.Frontiers in oncology · 2026Review
- Glutamine metabolism and its roles in tumor radiotherapy by regulating DNA damage repair.Frontiers in cell and developmental biology · 2026Review
- Article
- BCL-xL dependency in chromophobe renal cell carcinoma.Cancer gene therapy · 2025Article
- Tumor-Intrinsic and Microenvironmental Determinants of Impaired Antitumor Immunity in Chromophobe Renal Cell Carcinoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Article
- Prospects for ferroptosis therapies in cancer.Nature cancer · 2025Review
- Monotropein attenuates renal cell carcinoma cell progression and M2 macrophage polarization by weakening NF-κB.International urology and nephrology · 2025Article
- The pathogenesis and therapeutic implications of metabolic reprogramming in renal cell carcinoma.Cell death discovery · 2025Review
- Targeting ferroptosis in prostate cancer management: molecular mechanisms, multidisciplinary strategies and translational perspectives.Journal of translational medicine · 2025Review
- Regulation of Ferroptosis in Cancer and Immune Cells.Immune network · 2025Review
- Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Chromophobe (Ch) renal cell carcinoma (RCC) arises from the intercalated cell in the distal nephron. There are no proven treatments for metastatic ChRCC. A distinguishing characteristic of ChRCC is strikingly high levels of reduced (GSH) and oxidized (GSSG) glutathione. Here, we demonstrate that ChRCC-derived cells exhibit higher sensitivity to ferroptotic inducers compared with clear-cell RCC. ChRCC-derived cells are critically dependent on cystine via the cystine/glutamate antiporter xCT to maintain high levels of glutathione, making them sensitive to inhibitors of cystine uptake and cyst(e)inase. Gamma-glutamyl transferase 1 (GGT1), a key enzyme in glutathione homeostasis, is markedly suppressed in ChRCC relative to normal kidney. Importantly, GGT1 overexpression inhibits the proliferation of ChRCC cells in vitro and in vivo, suppresses cystine uptake, and decreases levels of GSH and GSSG. Collectively, these data identify ferroptosis as a metabolic vulnerability in ChRCC, providing a potential avenue for targeted therapy for these distinctive tumors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.