Academic Journal
Tissue of origin dictates branched-chain amino acid metabolism in mutant Kras-driven cancers
| العنوان: | Tissue of origin dictates branched-chain amino acid metabolism in mutant Kras-driven cancers |
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| المؤلفون: | Ji, B. W., Dixit, P. D., Wolpin, B. M., Vitkup, D., Mayers, Jared R., Torrence, Margaret E., Danai, Laura V., Papagiannakopoulos, Thales, Davidson, Shawn M., Bauer, Matthew R., Lau, Allison N., Hosios, Aaron Marc, Muir, Alexander, Chin, Christopher R., Freinkman, Elizaveta, Jacks, Tyler E., Vander Heiden, Matthew G. |
| المساهمون: | Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Mayers, Jared R., Torrence, Margaret E., Danai, Laura V., Papagiannakopoulos, Thales, Davidson, Shawn M., Bauer, Matthew R., Lau, Allison N., Hosios, Aaron Marc, Muir, Alexander, Chin, Christopher R., Freinkman, Elizaveta, Jacks, Tyler E., Vander Heiden, Matthew G. |
| المصدر: | PMC |
| بيانات النشر: | American Association for the Advancement of Science (AAAS) |
| سنة النشر: | 2018 |
| المجموعة: | DSpace@MIT (Massachusetts Institute of Technology) |
| الوصف: | Tumor genetics guides patient selection for many new therapies, and cell culture studies have demonstrated that specific mutations can promote metabolic phenotypes. However, whether tissue context defines cancer dependence on specific metabolic pathways is unknown. Kras activation and Trp53 deletion in the pancreas or the lung result in pancreatic ductal adenocarinoma (PDAC) or non-small cell lung carcinoma (NSCLC), respectively, but despite the same initiating events, these tumors use branched-chain amino acids (BCAAs) differently. NSCLC tumors incorporate free BCAAs into tissue protein and use BCAAs as a nitrogen source, whereas PDAC tumors have decreased BCAA uptake. These differences are reflected in expression levels of BCAA catabolic enzymes in both mice and humans. Loss of Bcat1 and Bcat2, the enzymes responsible for BCAA use, impairs NSCLC tumor formation, but these enzymes are not required for PDAC tumor formation, arguing that tissue of origin is an important determinant of how cancers satisfy their metabolic requirements. ; National Institutes of Health (U.S.) (Grant F30CA183474) ; National Institutes of Health (U.S.) (Grant T32GM007753) |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| تدمد: | 0036-8075 1095-9203 |
| Relation: | http://dx.doi.org/10.1126/SCIENCE.AAF5171; Science; http://hdl.handle.net/1721.1/116559; Mayers, J. R. et al. “Tissue of Origin Dictates Branched-Chain Amino Acid Metabolism in Mutant Kras-Driven Cancers.” Science 353, 6304 (September 2016): 1161–1165 © 2016 American Association for the Advancement of Science; orcid:0000-0002-8607-1787; orcid:0000-0002-8206-8003; orcid:0000-0001-9587-0233; orcid:0000-0003-4250-7355; orcid:0000-0002-7702-5877; orcid:0000-0001-5785-8911; orcid:0000-0002-6702-4192 |
| الاتاحة: | http://hdl.handle.net/1721.1/116559 |
| Rights: | Creative Commons Attribution-Noncommercial-Share Alike ; http://creativecommons.org/licenses/by-nc-sa/4.0/ |
| رقم الانضمام: | edsbas.688165E9 |
| قاعدة البيانات: | BASE |
| تدمد: | 00368075 10959203 |
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