ArticleOncogene2021
Wild-type IDH2 protects nuclear DNA from oxidative damage and is a potential therapeutic target in colorectal cancer.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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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
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- ATM is associated with the prognosis of colorectal cancer: a systematic review.Frontiers in oncology · 2025Pooled it
- Exosome-delivered pepDCBLD2 promotes glucose metabolism to induce chemoresistance in colon cancer.Journal of translational medicine · 2026Article
- Advancements in targeted therapies for acute myeloid leukemia.Current opinion in pharmacology · 2026Review
- MTHFD2-mediated redox homeostasis promotes gastric cancer progression under hypoxic conditions.Redox report : communications in free radical research · 2024Article
- Article
- Interplay Between Skeletal and Hematopoietic Cells in the Bone Marrow Microenvironment in Homeostasis and Aging.Current osteoporosis reports · 2024Review
- Targeting ROS in cancer: rationale and strategies.Nature reviews. Drug discovery · 2024Review
- SIRT5-mediated ME2 desuccinylation promotes cancer growth by enhancing mitochondrial respiration.Cell death and differentiation · 2024Article
- Wild-type IDH1 Knockout Leads to G0/G1 Arrest, Impairs Cancer Cell Proliferation, Altering Glycolysis, and the TCA Cycle in Colon Cancer.Biochemical genetics · 2023Article
- Genetic mutations affecting mitochondrial function in cancer drug resistance.Genes & genomics · 2023Review
- Metabolic reprogramming in colorectal cancer: regulatory networks and therapy.Cell & bioscience · 2023Review
- Targeting Mitochondrial IDH2 Enhances Antitumor Activity of Cisplatin in Lung Cancer via ROS-Mediated Mechanism.Biomedicines · 2023Article
- IDH2, a novel target of OGT, facilitates glucose uptake and cellular bioenergy production via NF-κB signaling to promote colorectal cancer progression.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- Genetics of enzymatic dysfunctions in metabolic disorders and cancer.Frontiers in oncology · 2023Review
- Effects of cancer-associated point mutations on the structure, function, and stability of isocitrate dehydrogenase 2.Scientific reports · 2022Article
- Reductive TCA cycle catalyzed by wild-type IDH2 promotes acute myeloid leukemia and is a metabolic vulnerability for potential targeted therapy.Journal of hematology & oncology · 2022Article
- The Molecular Mechanisms of Resistance to IDH Inhibitors in Acute Myeloid Leukemia.Frontiers in oncology · 2022Review
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 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although the role of isocitrate dehydrogenase (IDH) mutation in promoting cancer development has been well-characterized, the impact of wild-type IDH on cancer cells remains unclear. Here we show that the wild-type isocitrate dehydrogenase 2 (IDH2) is highly expressed in colorectal cancer (CRC) cells, and plays an unexpected role in protecting the cancer cells from oxidative damage. Genetic abrogation of IDH2 in CRC cells leads to reactive oxygen species (ROS)-mediated DNA damage and an accumulation of 8-oxoguanine with DNA strand breaks, which activates DNA damage response (DDR) with elevated γH2AX and phosphorylation of ataxia telangiectasia-mutated (ATM) protein, leading to a partial cell cycle arrest and eventually cell senescence. Mechanistically, the suppression of IDH2 results in a reduction of the tricarboxylic acid (TCA) cycle activity due to a decrease in the conversion of isocitrate to α-ketoglutarate (α-KG) with a concurrent decrease in NADPH production, leading to ROS accumulation and oxidative DNA damage. Importantly, abrogation of IDH2 inhibits CRC cell growth in vitro and in vivo, and renders CRC cells more vulnerable to DNA-damaging drugs. Screening of an FDA-approved drug library has identified oxaliplatin as a compound highly effective against CRC cells when IDH2 was suppressed. Our study has uncovered an important role of the wild-type IDH2 in protecting DNA from oxidative damage, and provides a novel biochemical basis for developing metabolic intervention strategy for cancer treatment.
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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 OpenQuestion graph.