ArticleOncogene2015
MutT Homolog 1 (MTH1) maintains multiple KRAS-driven pro-malignant pathways.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 92 citations in OpenAlex.
- Nucleotide salvage, genome instability, and potential therapeutic applications.Nucleic acids research · 2026Review
- Loss of MicroRNA-29b promotes DNMT3b-mediated STING downregulation to attenuate radiotherapy-induced antitumor immunity in KRAS-mutated colorectal cancer.NPJ precision oncology · 2026Article
- Repurposing resveratrol for redox-mediated inhibition of MTH1 in breast cancer.Scientific reports · 2025Article
- Blood metabolites, mitochondrial biofunction, and cervical cancer: a bidirectional Mendelian randomization study.BMC women's health · 2025Article
- Clinical Significance of NUDT1 (MTH1) Across Cancer Types.International journal of molecular sciences · 2025Review
- Role of MTH1 in oxidative stress and therapeutic targeting of cancer.Redox biology · 2024Review
- Oxidative stress is two-sided in the treatment of acute myeloid leukemia.Cancer medicine · 2024Review
- Light-Elicited and Oxygen-Saved Iridium Nanocapsule for Oxidative Damage Intensified Oncotherapy.Molecules (Basel, Switzerland) · 2023Article
- Mitotic MTH1 Inhibitors in Treatment of Cancer.Cancer treatment and research · 2023Article
- Progress in Anticancer Drug Development Targeting Ubiquitination-Related Factors.International journal of molecular sciences · 2022Review
- Article
- MTH1 Inhibitor TH1579 Induces Oxidative DNA Damage and Mitotic Arrest in Acute Myeloid Leukemia.Cancer research · 2021Article
- Oncogenic KRAS drives radioresistance through upregulation of NRF2-53BP1-mediated non-homologous end-joining repair.Nucleic acids research · 2021Article
- HIF2α promotes tumour growth in clear cell renal cell carcinoma by increasing the expression of NUDT1 to reduce oxidative stress.Clinical and translational medicine · 2021Article
- A Double-Edged Sword: The Anti-Cancer Effects of Emodin by Inhibiting the Redox-Protective Protein MTH1 and Augmenting ROS in NSCLC.Journal of Cancer · 2021Article
- Targeting human MutT homolog 1 (MTH1) for cancer eradication: current progress and perspectives.Acta pharmaceutica Sinica. B · 2020Review
- AXL and CAV-1 play a role for MTH1 inhibitor TH1579 sensitivity in cutaneous malignant melanoma.Cell death and differentiation · 2020Article
- MTH1 favors mesothelioma progression and mediates paracrine rescue of bystander endothelium from oxidative damage.JCI insight · 2020Article
- Caveolin-1, a master regulator of cellular senescence.Cancer metastasis reviews · 2020Review
- The Existence of MTH1-independent 8-oxodGTPase Activity in Cancer Cells as a Compensatory Mechanism against On-target Effects of MTH1 Inhibitors.Molecular cancer therapeutics · 2020Article
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Oncogenic RAS promotes production of reactive oxygen species (ROS), which mediate pro-malignant signaling but can also trigger DNA damage-induced tumor suppression. Thus RAS-driven tumor cells require redox-protective mechanisms to mitigate the damaging aspects of ROS. Here, we show that MutT Homolog 1 (MTH1), the mammalian 8-oxodGTPase that sanitizes oxidative damage in the nucleotide pool, is important for maintaining several KRAS-driven pro-malignant traits in a nonsmall cell lung carcinoma (NSCLC) model. MTH1 suppression in KRAS-mutant NSCLC cells impairs proliferation and xenograft tumor formation. Furthermore, MTH1 levels modulate KRAS-induced transformation of immortalized lung epithelial cells. MTH1 expression is upregulated by oncogenic KRAS and correlates positively with high KRAS levels in NSCLC human tumors. At a molecular level, in p53-competent KRAS-mutant cells, MTH1 loss provokes DNA damage and induction of oncogene-induced senescence. In p53-nonfunctional KRAS-mutant cells, MTH1 suppression does not produce DNA damage but reduces proliferation and leads to an adaptive decrease in KRAS expression levels. Thus, MTH1 not only enables evasion of oxidative DNA damage and its consequences, but can also function as a molecular rheostat for maintaining oncogene expression at optimal levels. Accordingly, our results indicate MTH1 is a novel and critical component of oncogenic KRAS-associated malignancy and its inhibition is likely to yield significant tumor-suppressive outcomes in KRAS-driven tumors.
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