ArticleProceedings of the National Academy of Sciences of the United States of America2014
mTOR target NDRG1 confers MGMT-dependent resistance to alkylating chemotherapy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 110 papers, 1 of them a synthesis that pooled it.
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Who cites it
110 citing papers in PubMed, 1 synthesis or guideline pooled it, 196 citations in OpenAlex.
- NDRG1 regulates neutral lipid metabolism in breast cancer cells.Breast cancer research : BCR · 2018Pooled it
- Proximity ligation assay evaluates IDH1R132H presentation in gliomas.The Journal of clinical investigation · 2015Trial
- Cancer-associated fibroblasts regulate DNA repair in pancreatic cancer through NDRG1-mediated R-loop processing.Nature cell biology · 2026Article
- Article
- Phosphorylation disrupts the interaction between the intrinsically disordered region of the oncogenic NDRG1 and lipid vesicles.Protein science : a publication of the Protein Society · 2026Article
- Multi-transcriptomics reveals niche-specific expression programs and endothelial cells in glioblastoma.Journal of translational medicine · 2025Article
- Insight into the Regulation of NDRG1 Expression.International journal of molecular sciences · 2025Review
- Vaccine-induced T cell receptor T cell therapy targeting a glioblastoma stemness antigen.Nature communications · 2025Article
- MAPK14/p38α shapes the molecular landscape of endometrial cancer and promotes tumorigenic characteristics.Cell reports · 2025Article
- The genetic architecture of bone metastases: unveiling the role of epigenetic and genetic modifications in drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Signature-based repurposed drugs resemble the inhibition of TGFβ-induced NDRG1 as potential therapeutics for triple-negative breast cancer.International journal of biological sciences · 2025Article
- Transkingdom mechanism of MAMP generation by chitotriosidase feeds oligomeric chitin from fungal pathogens and allergens into TLR2-mediated innate immune sensing.Frontiers in immunology · 2025Article
- Disrupting glioblastoma networks with tumor treating fields (TTFields) in in vitro models.Journal of neuro-oncology · 2024Article
- MEN1 Deficiency-Driven Activation of the β-Catenin-MGMT Axis Promotes Pancreatic Neuroendocrine Tumor Growth and Confers Temozolomide Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- NSUN6-mediated 5-methylcytosine modification of NDRG1 mRNA promotes radioresistance in cervical cancer.Molecular cancer · 2024Article
- 'The Reports of My Death Are Greatly Exaggerated'-Evaluating the Effect of Necrosis onCancers · 2024Article
- OiScience · 2024Article
- Germ line variant GFI1-36N affects DNA repair and sensitizes AML cells to DNA damage and repair therapy.Blood · 2023Article
- MAOA suppresses the growth of gastric cancer by interacting with NDRG1 and regulating the Warburg effect through the PI3K/AKT/mTOR pathway.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- mTOR Signaling Pathway and Gut Microbiota in Various Disorders: Mechanisms and Potential Drugs in Pharmacotherapy.International journal of molecular sciences · 2023Review
50 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
28 authors at 10 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A hypoxic microenvironment induces resistance to alkylating agents by activating targets in the mammalian target of rapamycin (mTOR) pathway. The molecular mechanisms involved in this mTOR-mediated hypoxia-induced chemoresistance, however, are unclear. Here we identify the mTOR target N-myc downstream regulated gene 1 (NDRG1) as a key determinant of resistance toward alkylating chemotherapy, driven by hypoxia but also by therapeutic measures such as irradiation, corticosteroids, and chronic exposure to alkylating agents via distinct molecular routes involving hypoxia-inducible factor (HIF)-1alpha, p53, and the mTOR complex 2 (mTORC2)/serum glucocorticoid-induced protein kinase 1 (SGK1) pathway. Resistance toward alkylating chemotherapy but not radiotherapy was dependent on NDRG1 expression and activity. In posttreatment tumor tissue of patients with malignant gliomas, NDRG1 was induced and predictive of poor response to alkylating chemotherapy. On a molecular level, NDRG1 bound and stabilized methyltransferases, chiefly O(6)-methylguanine-DNA methyltransferase (MGMT), a key enzyme for resistance to alkylating agents in glioblastoma patients. In patients with glioblastoma, MGMT promoter methylation in tumor tissue was not more predictive for response to alkylating chemotherapy in patients who received concomitant corticosteroids.
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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.