The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Disordered methionine metabolism in MTAP/CDKN2A-deleted cancers leads to dependence on PRMT5
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
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“Loss of MTAP expression can result in another vulnerability for cancer cells because the MTA that accumulates following MTAP loss can act as a potent inhibitor of the enzyme arginine methyltransferase 5 (PRMT5).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Mavrakis et al., 2016
In the citing paper
“Deletion of the tumor suppressor CDKN2A results in concomitant deletion of the methionine salvage pathway enzyme methylthioadenosine phosphorylase (MTAP) in many cancers, including 53% of glioblastomas and 26% of pancreatic cancers (Mavrakis et al., 2016).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Mavrakis et al., 2016
In the citing paper
“MTAP loss results in reduced PRMT5 activity and renders MTAP-null cancer cell more sensitive to PRMT5 depletion than isogenic counterparts that express MTAP (Kryukov et al., 2016; Marjon et al., 2016; Mavrakis et al., 2016).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Mavrakis et al., 2016
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Metadata
- Authors
- Mavrakis, K. J., McDonald, E. R., Schlabach, M. R., Billy, E., Hoffman, G. R., deWeck, A., Ruddy, D. A., Venkatesan, K., Yu, J., McAllister, G., Stump, M., deBeaumont, R., Ho, S., Yue, Y., Liu, Y., Yan-Neale, Y., Yang, G., Lin, F., Yin, H., Gao, H., Kipp, D. R., Zhao, S., McNamara, J. T., Sprague, E. R., Zheng, B., Lin, Y., Cho, Y. S., Gu, J., Crawford, K., Ciccone, D., Vitari, A. C., Lai, A., Capka, V., Hurov, K., Porter, J. A., Tallarico, J., Mickanin, C., Lees, E., Pagliarini, R., Keen, N., Schmelzle, T., Hofmann, F., Stegmeier, F., & Sellers, W. R.
- Affiliations
- Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA.
- Novartis Institutes for Biomedical Research, Basel CH-4002, Switzerland.
- Novartis Institutes for Biomedical Research, Emeryville, CA 94608, USA.
- Novartis (China) (CN)
- Novartis Institutes for BioMedical Research (CH)
- Corresponding author
- Mavrakis, Konstantinos J.
- McDonald, E. Robert
- Schlabach, Michael R.
- Hoffman, Gregory R.
- Schmelzle, Tobias
- Hofmann, Francesco
- Stegmeier, Frank
- Sellers, William R.
- ORCID
- McDonald, E. Robert
- Schlabach, Michael R.
- Ruddy, David A.
- Venkatesan, Kavitha
- Yu, Jianjun
- Ho, Samuel
- Liu, Yue
- Yin, Hong
- Kipp, D. Randal
- Zhao, Songping
- McNamara, Joshua T.
- Sprague, Elizabeth R.
- Lin, Ying
- Cho, Young Shin
- Ciccone, David
- Lai, Albert
- Tallarico, John
- Lees, Emma
- Pagliarini, Raymond
- Keen, Nicholas
- Schmelzle, Tobias
- Stegmeier, Frank
- Sellers, William R.
- Venue
- Science
- Published
- 2016-03-11
- Volume
- 351
- Issue
- 6278
- Pages
- 1208-1213
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2287840388
- Cited by
- 607
- References
- 29
- Citations by year
- 2026: 86 · 2025: 96 · 2024: 72 · 2023: 54 · 2022: 58 · 2021: 48 · 2020: 40 · 2019: 50 · 2018: 39 · 2017: 37 · 2016: 25
- FWCI
- 26.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Office of Science, Office of Basic Energy Sciences, U.S. Department of Energy (DE-AC02-06CH11357)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Keywords
- MTAP, CDKN2A, PRMT5, methylthioadenosine, methionine salvage pathway, methionine metabolism, cancer cell lines, PRMT5 inhibition, tumor suppressor loss, cancer metabolism, targeted cancer therapy
- MeSH terms
- Cell Survival, Deoxyadenosines, Humans, Methionine, Neoplasms, Protein-Arginine N-Methyltransferases, Purine-Nucleoside Phosphorylase, Thionucleosides, Gene Deletion, Cyclin-Dependent Kinase Inhibitor p16, RNA, Small Interfering, Cell Line, Tumor
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