克拉斯
癌症研究
生物
表型
酶
胰腺
胰腺癌
背景(考古学)
分解代谢
癌症
突变
内科学
新陈代谢
氨基酸
生物化学
遗传学
医学
基因
古生物学
作者
Jared R. Mayers,Margaret E. Torrence,Laura V. Danai,Thales Papagiannakopoulos,Shawn M. Davidson,Matthew R. Bauer,Allison N. Lau,Brian W. Ji,Purushottam D. Dixit,Aaron M. Hosios,Alexander Muir,Christopher R. Chin,Elizaveta Freinkman,Tyler Jacks,Brian M. Wolpin,Dennis Vitkup,Matthew G. Vander Heiden
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2016-09-09
卷期号:353 (6304): 1161-1165
被引量:442
标识
DOI:10.1126/science.aaf5171
摘要
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.
科研通智能强力驱动
Strongly Powered by AbleSci AI