1. Disordered methionine metabolism in MTAP/CDKN2A-deleted cancers leads to dependence on PRMT5
- Author
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D. Randal Kipp, Craig Mickanin, Jeffery A. Porter, Albert Lai, Bing Zheng, Mark Stump, Yan Yan-Neale, John A. Tallarico, Young Shin Cho, Gregory R. Hoffman, Tobias Schmelzle, William R. Sellers, Samuel B. Ho, E. Robert McDonald, Kavitha Venkatesan, Yue Liu, Songping Zhao, Rosalie deBeaumont, Eric Billy, Ying Lin, Francesco Hofmann, Konstantinos J. Mavrakis, Vladimir Capka, Jianjun Yu, Antoine deWeck, Joshua T. McNamara, Emma Lees, Michael R. Schlabach, Hui Gao, Elizabeth R. Sprague, Nicholas Keen, Kristen Hurov, Kenneth Crawford, David A. Ruddy, David N. Ciccone, Guizhi Yang, Fallon Lin, Gregg McAllister, Justin Gu, Raymond Pagliarini, Alberto C. Vitari, Frank Stegmeier, Yingzi Yue, and Hong Yin
- Subjects
0301 basic medicine ,Multidisciplinary ,Methyltransferase ,Methionine ,Tumor suppressor gene ,Protein arginine methyltransferase 5 ,Purine nucleoside phosphorylase ,Biology ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,chemistry ,Biochemistry ,CDKN2A ,Cell culture ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research - Abstract
Tumors put in a vulnerable position Cancer cells often display alterations in metabolism that help fuel their growth. Such metabolic “rewiring” may also work against the cancer cells, however, by creating new vulnerabilities that can be exploited therapeutically. A variety of human tumors show changes in methionine metabolism caused by loss of the gene coding for 5-methylthioadenosine phosphorylase (MTAP). Mavrakis et al. and Kryukov et al. found that the loss of MTAP renders cancer cell lines sensitive to growth inhibition by compounds that suppress the activity of a specific arginine methyltransferase called PRMT5. Conceivably, drugs that inhibit PRMT5 activity could be developed into a tailored therapy for MTAP-deficient tumors. Science , this issue pp. 1208 and 1214
- Published
- 2016
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