期刊
CANCER RESEARCH
卷 81, 期 5, 页码 1252-1264出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-20-1847
关键词
-
类别
资金
- NIH NCI [DP2 CA249950-01, T32 CA009171]
- W.W. Smith Charitable Trust
- Susan G. Komen [CCR19608782]
- V Foundation for Cancer Research
- NIH [P30 CA010815, R50 CA221838, S10 OD023586]
ACSS2 is a crucial enzyme in cancer cells that helps them use acetate as an alternative nutrient source under stress. Inhibiting ACSS2 has been shown to effectively inhibit tumor growth.
Acetyl-CoA is a vitally important and versatile metabolite used for many cellular processes including fatty acid synthesis, ATP production, and protein acetylation. Recent studies have shown that cancer cells upregulate acetyl-CoA synthetase 2 (ACSS2), an enzyme that converts acetate to acetyl-CoA, in response to stresses such as low nutrient availability and hypoxia. Stressed cancer cells use ACSS2 as a means to exploit acetate as an alternative nutrient source. Genetic depletion of ACSS2 in tumors inhibits the growth of a wide variety of cancers. However, there are no studies on the use of an ACSS2 inhibitor to block tumor growth. In this study, we synthesized a small-molecule inhibitor that acts as a transition-state mimetic to block ACSS2 activity in vitro and in vivo. Pharmacologic inhibition of ACSS2 as a single agent impaired breast tumor growth. Collectively, our findings suggest that targeting ACSS2 may be an effective therapeutic approach for the treatment of patients with breast cancer. Significance: These findings suggest that targeting acetate metabolism through ACSS2 inhibitors has the potential to safely and effectively treat a wide range of patients with cancer.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据