ArticleAntioxidants & redox signaling2014
The PTEN/NRF2 axis promotes human carcinogenesis.
Article in Antioxidants & redox signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 2 of them syntheses that pooled it.
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Who cites it
84 citing papers in PubMed, 2 syntheses or guidelines pooled it, 132 citations in OpenAlex.
- Drug repurposing on Alzheimer's disease through modulation of NRF2 neighborhood.Redox biology · 2023Pooled it
- Insight into Nrf2: a bibliometric and visual analysis from 2000 to 2022.Frontiers in genetics · 2023Pooled it
- Interplay between NRF2 post-translational modifications and protein-protein interactions: Perspectives from emerging structural and functional evidence.Archives of biochemistry and biophysics · 2026Review
- NRF2 as a guardian of health: from an ancient survival pathway to a modern therapeutic target.Redox biology · 2026Review
- Nrf2 signaling pathway and its molecular regulatory mechanism.Journal of Zhejiang University. Science. B · 2026Review
- Hexaraphane as a potential therapeutic strategy for tauopathies.Redox biology · 2026Article
- Targeting ubiquitin signaling vulnerabilities in KEAP1-inactivated lung cancer.The EMBO journal · 2026Article
- LRRC8A Inhibition Overcomes Chemoresistance by Downregulating MRP3 and CYP3A4 in the 3D Spheroid Model of Human Breast Cancer Cells.International journal of molecular sciences · 2026Article
- FBXO22 promotes hepatocellular carcinoma progression via paracrine myo‑inositol‑induced M2‑type polarization of macrophages.International journal of molecular medicine · 2026Article
- Modulation of the Receptor Tyrosine Kinase TIE2/International journal of molecular sciences · 2026Article
- Targeting DPP9 attenuates podocyte injury by regulating NRF2 antioxidant signaling.Frontiers in pharmacology · 2026Article
- The PI3K pathway is a downstream effector of NRF2 activation in the esophagus.Translational oncology · 2026Article
- Proteomic Analysis of PTEN-Deficient Cells Reveals Src-Mediated Upregulation of EphA2 and Therapeutic Potential of Dual Inhibition.Molecular & cellular proteomics : MCP · 2025Article
- A novel β-TrCP1/NRF2 interaction inhibitor for effective anti-inflammatory therapy.Journal of biomedical science · 2025Article
- SCD1 Inhibition Blocks the AKT-NRF2-SLC7A11 Pathway to Induce Lipid Metabolism Remodeling and Ferroptosis Priming in Lung Adenocarcinoma.Cancer research · 2025Article
- Based on single-cell and transcriptome data, ferroptosis and the immunological landscape in osteosarcoma were discovered.Discover oncology · 2025Article
- Huangkui capsules regulate tryptophan metabolism to improve diabetic nephropathy through the Keap1/Nrf2/HO-1 pathway.Frontiers in pharmacology · 2025Article
- Review
- Specific targeting of the NRF2/β-TrCP axis promotes beneficial effects in NASH.Redox biology · 2024Article
- Nrf2-Mediated Antioxidant Response and Drug Efflux Transporters Upregulation as Possible Mechanisms of Resistance in Photodynamic Therapy of Cancers.OncoTargets and therapy · 2024Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsA recent study conducted in mice reported that liver-specific knockout of tumor suppressor Pten augments nuclear factor (erythroid-derived 2)-like 2 (NRF2) transcriptional activity. Here, we further investigated how phosphatase and tensin homolog deleted on chromosome 10 (PTEN) controls NRF2 and the relevance of this pathway in human carcin ogenesis.
resultsDrug and genetic targeting to PTEN and phosphoproteomics approaches indicated that PTEN leads to glycogen synthase kinase-3 (GSK-3)-mediated phosphorylation of NRF2 at residues Ser(335) and Ser(338) and subsequent beta-transducin repeat containing protein (β-TrCP)-dependent but Kelch-like ECH-associated protein 1 (KEAP1)-independent degradation. Rescue experiments in PTEN-deficient cells and xerographs in athymic mice indicated that loss of PTEN leads to increased NRF2 signature which provides a proliferating and tumorigenic advantage. Tissue microarrays from endometrioid carcinomas showed that 80% of PTEN-negative tumors expressed high levels of NRF2 or its target heme oxygenase-1 (HO-1). INNOVATION: These results uncover a new mechanism of oncogenic activation of NRF2 by loss of its negative regulation by PTEN/GSK-3/β-TrCP that may be relevant to a large number of tumors, including endometrioid carcinomas.
conclusionIncreased activity of NRF2 due to loss of PTEN is instrumental in human carcinogenesis and represents a novel therapeutic target.
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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 OpenQuestion graph.