ArticleProceedings of the National Academy of Sciences of the United States of America2018
Impairment of gamma-glutamyl transferase 1 activity in the metabolic pathogenesis of chromophobe renal cell carcinoma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 2 of them syntheses that pooled it.
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Who cites it
54 citing papers in PubMed, 2 syntheses or guidelines pooled it, 78 citations in OpenAlex.
- From Gene to Enzyme: Multidimensional Decoding of the GGT Molecular Family and Its Clinical Tumor Diagnosis.Cancer medicine · 2025Pooled it
- A multimodal atlas of tumour metabolism reveals the architecture of gene-metabolite covariation.Nature metabolism · 2023Pooled it
- Exploring regulated cell death in renal cell carcinoma: mechanistic insights and therapeutic perspectives.Apoptosis : an international journal on programmed cell death · 2026Review
- Reviving cancer vaccines in renal cell carcinoma: a new chapter in immunotherapy for kidney cancer.Immuno-oncology technology · 2026Review
- mTORC1 activation induces B7-H3-dependent metabolic reprogramming in renal cell carcinoma (RCC).Oncogene · 2026Article
- Maternal liver function and adverse pregnancy outcomes in Chinese women with HIV: a cohort study.BMC public health · 2026Article
- Article
- Advancing early detection of chromophobe renal cell carcinoma: a Bayesian optimization approach to machine learning models.Scientific reports · 2026Article
- A Mitochondrial Plasma Proteomic Signature Identifies Metastatic Chromophobe Renal Cell Carcinoma.Cancers · 2026Article
- 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
- Metabolomics for the Identification of Biomarkers in Kidney Diseases.Nanotheranostics · 2025Review
- Causal impact of genetically determined metabolites on kidney cancer and its subtypes: an integrated mendelian randomization and metabolomic study.American journal of cancer research · 2025Article
- TFE3 fusions direct an oncogenic transcriptional program that drives OXPHOS and unveils vulnerabilities in translocation renal cell carcinoma.bioRxiv : the preprint server for biology · 2024Article
- Metabolomic landscape of renal cell carcinoma in von Hippel-Lindau syndrome in a Chinese cohort.iScience · 2024Article
- Renal Cell Carcinoma of Variant Histology: New Biologic Understanding Leads to Therapeutic Advances.American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting · 2024Review
- Metabolic alterations in hereditary and sporadic renal cell carcinoma.Nature reviews. Nephrology · 2024Review
- The 5th Kidney Cancer Research Summit: Research Accelerating Cures for Renal Cell Carcinoma in 2023.The oncologist · 2024Article
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Authors and funding
12 authors at 6 institutions in 1 country.
Funding
Abstract
Chromophobe renal cell carcinoma (ChRCC) accounts for 5% of all sporadic renal cancers and can also occur in genetic syndromes including Birt-Hogg-Dube (BHD) and tuberous sclerosis complex (TSC). ChRCC has a distinct accumulation of abnormal mitochondria, accompanied by characteristic chromosomal imbalances and relatively few "driver" mutations. Metabolomic profiling of ChRCC and oncocytomas (benign renal tumors that share pathological features with ChRCC) revealed both similarities and differences between these tumor types, with principal component analysis (PCA) showing a distinct separation. ChRCC have a striking decrease in intermediates of the glutathione salvage pathway (also known as the gamma-glutamyl cycle) compared with adjacent normal kidney, as well as significant changes in glycolytic and pentose phosphate pathway intermediates. We also found that gamma glutamyl transferase 1 (GGT1), the key enzyme of the gamma-glutamyl cycle, is expressed at ∼100-fold lower levels in ChRCC compared with normal kidney, while no change in GGT1 expression was found in clear cell RCC (ccRCC). Significant differences in specific metabolite abundance were found in ChRCC vs. ccRCC, including the oxidative stress marker ophthalmate. Down-regulation of GGT1 enhanced the sensitivity to oxidative stress and treatment with buthionine sulfoximine (BSO), which was associated with changes in glutathione-pathway metabolites. These data indicate that impairment of the glutathione salvage pathway, associated with enhanced oxidative stress, may have key therapeutic implications for this rare tumor type for which there are currently no specific targeted therapies.
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