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NDRG1 expression in cancers confers dependence on DNA damage repair and sensitivity to quinacrine
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DOI：10.1126/scisignal.adv4272.png)
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Abstract
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DNA damage repair is essential to cell survival, making it an attractive target for cancer therapy. Mkrtchyan et al. identified a therapeutically exploitable role for the stress-response protein NDRG1 in the DNA damage response (DDR). High-throughput screens revealed that high NDRG1 expression in cancer cell lines correlated with sensitivity to the antimalarial drug quinacrine, which impaired the ubiquitylation-dependent recruitment of a critical DDR protein to sites of DNA damage. Colorectal cancer cells with mutations in the DNA repair–associated genes MLH1 and PARP3 were particularly sensitive to quinacrine or NDRG1 knockdown. The findings reveal potential strategies to target the DDR based on NDRG1 expression. —Leslie K. Ferrarelli
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