ArticleOncotarget2017
Keap1/Nrf2 pathway in kidney cancer: frequent methylation of KEAP1 gene promoter in clear renal cell carcinoma.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- KEAP1 promoter hypermethylation in human cancers: a meta-analysis of case-control studies.International journal of clinical oncology · 2026Pooled it
- TSC22D4 drives clear cell renal cell carcinoma progression and therapy resistance by stabilizing NRF2 through KEAP1 disruption.Cell death & disease · 2026Article
- Differential NRF2 Methylation and PD-1 Expression in Normal Tissues of Colorectal Adenoma and Carcinoma across Sexes.The world journal of men's health · 2026Article
- Sex-Specific Molecular Markers NRF2 and PD-L1 in Colon Carcinogenesis: Implications for Right-Sided Colon Cancer.Cancer research and treatment · 2025Article
- Review
- An organoid library of human esophageal squamous cell carcinomas (ESCCs) uncovers the chemotherapy-resistant ESCC features.Communications biology · 2025Article
- Article
- Nrf2 Signaling in Renal Cell Carcinoma: A Potential Candidate for the Development of Novel Therapeutic Strategies.International journal of molecular sciences · 2024Review
- Specific cancer types and prognosis in patients with variations in the KEAP1-NRF2 system: A retrospective cohort study.Cancer science · 2024Article
- A framework for target discovery in rare cancers.bioRxiv : the preprint server for biology · 2024Article
- Toward a CRISPR-based mouse model ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Pterostilbene Reverses Epigenetic Silencing of Nrf2 and Enhances Antioxidant Response in Endothelial Cells in Hyperglycemic Microenvironment.Nutrients · 2024Article
- Article
- Effects ofCancers · 2024Article
- The Growth Inhibitory Effect of Resveratrol and Gallic Acid on Prostate Cancer Cell Lines through the Alteration of Oxidative Stress Balance: The Interplay betweenAnti-cancer agents in medicinal chemistry · 2024Article
- Keap1-Nrf2 pathway: a key mechanism in the occurrence and development of cancer.Frontiers in oncology · 2024Review
- Regulation of Cell Proliferation and Nrf2-Mediated Antioxidant Defense: Conservation of Keap1 Cysteines and Nrf2 Binding Site in the Context of the Evolution of KLHL Family.Life (Basel, Switzerland) · 2023Article
- Post-translational modifications of Keap1: the state of the art.Frontiers in cell and developmental biology · 2023Review
- The KEAP1-NRF2 System and Esophageal Cancer.Cancers · 2022Review
- NRF2: KEAPing Tumors Protected.Cancer discovery · 2022Article
Corrections and comments
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Authors and funding
24 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Keap1/Nrf2 pathway is a master regulator of the cellular redox state through the induction of several antioxidant defence genes implicated in chemotherapeutic drugs resistance of tumor cells. An increasing body of evidence supports a key role for Keap1/Nrf2 pathway in kidney diseases and renal cell carcinoma (RCC), but data concerning the molecular basis and the clinical effect of its deregulation remain incomplete.Here we present a molecular profiling of the KEAP1 and NFE2L2 genes in five different Renal Cell Carcinoma histotypes by analysing 89 tumor/normal paired tissues (clear cell Renal Carcinoma, ccRCCs; Oncocytomas; Papillary Renal Cell Carcinoma Type 1, PRCC1; Papillary Renal Cell Carcinoma Type 2, PRCC2; and Chromophobe Cell Carcinoma).A tumor-specific DNA methylation of the KEAP1 gene promoter region was found as a specific feature of the ccRCC subtype (18/37, 48.6%) and a direct correlation with mRNA levels was confirmed by in vitro 5-azacytidine treatment. Analysis of an independent data set of 481 ccRCC and 265 PRCC tumors corroborates our results and multivariate analysis reveals a significant correlation among ccRCCs epigenetic KEAP1 silencing and staging, grading and overall survival.Our molecular results show for the the first time the epigenetic silencing of KEAP1 promoter as the leading mechanism for modulation of KEAP1 expression in ccRCCs and corroborate the driver role of Keap1/Nrf2 axis deregulation with potential new function as independent epigenetic prognostic marker in renal cell carcinoma.
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