MTH1

Supporting information

MTH1 (MutT homolog-1; NUDT1), EC 3.6.1.56, is an oxidized purine nucleoside triphosphatase, which is part of the Nudix hydrolase family. MTH1 hydrolyzes cytotoxic oxidized nucleoside triphosphates (dNTPs), such as 2-OH-dATP, preventing them from becoming mis-incorporated into DNA during replication or repair, thus promoting cell survival.

Redox dysfunction is common in cancer cells, owing to their altered metabolism. This results in an excess of reactive oxygen species (ROS), which damage free dNTPs. By preventing the oxidized dNTPs from corrupting the cell's DNA, MTH1 promotes tumorigenesis, cancer progression and apoptosis evasion. Cancer cells, unlike normal cells, are proposed to depend on MTH1 activity for survival, making it an attractive therapeutic target because it is cancer phenotypically lethal. Furthermore free dNTPs are significantly more susceptible than DNA to this type of oxidative damage, so targeting dNTPs may be an efficient method of encouraging replicative stress, reducing proliferation and inducing apoptosis in cancer cells.

In addition to its role in the evasion of DNA damage, MTH1 also plays a role in maintaining many KRAS-driven malignant traits in nonsmall cell lung carcinoma (NSCLC). In support of this, there is a strong association between MTH1 and KRAS expression levels, with suppression of MTH1 resulting in decreased KRAS levels, and a reduction in KRAS-driven malignancy, although these outcomes are influenced by the cells' p53 status.

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Gene Species Gene Symbol Gene Accession No. Protein Accession No.
NUDT1 Human EIF2AK3 NM_002452 P36639
Mouse Eif2ak3 NM_008637 P53368
Rat Eif2ak3 NM_057120 NP_476461

Literature for MTH1

Cancer Research Product Guide

A collection of over 750 products for cancer research, the guide includes research tools for the study of:

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Cancer Metabolism Life Science Poster

Genetic changes and epigenetic modifications in cancer cells alter the regulation of cellular metabolic pathways. These distinct metabolic circuits could provide viable cancer therapeutic targets. Adapted from the 2015 Cancer Product Guide, Edition 3, this poster summarizes the main targets for cancer metabolism researchers.

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Cancer Metabolism Life Science Poster
Epigenetics in Cancer Life Science Poster

The dysregulation of epigenetic modifications has been shown to result in oncogenesis and cancer progression. Unlike genetic mutations, epigenetic alterations are considered to be reversible and thus make promising therapeutic targets. Adapted from the 2015 Cancer Product Guide Edition 3, this poster summarizes the main epigenetic targets in cancer.

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Epigenetics in Cancer Life Science Poster

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Cancer Research Product Guide

Cancer Research Product Guide

Our Cancer Research Guide highlights over 750 products for cancer research. Request copy or view PDF today.

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Cancer Metabolism Life Science Poster

Taken from the Cancer Product Guide Edition 3

Cancer Metabolism Life Science Poster

Our Cancer Metabolism poster summarizes the main metabolic pathways in cancer cells, and highlights potential targets for cancer therapeutics. Request copy or view PDF today.

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Epigenetics in Cancer Life Science Poster

Taken from the Cancer Product Guide Edition 3

Epigenetics in Cancer Life Science Poster

Our Epigenetics in Cancer poster summarizes the main epigenetic targets in cancer, and highlights chemical compounds for the inhibition of these targets. Request copy or view PDF today.

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