Glutamine-utilizing transaminases are a metabolic vulnerability of TAZ/YAP-activated cancer cells

doi:10.15252/embr.201643577

	Glutamine-utilizing transaminases are a metabolic vulnerability of TAZ/YAP-activated cancer cells
	Yang, Chih-Sheng 1; Stampouloglou, Eleni 1; Kingston, Nathan M.1; Zhang, Liye2,3 ; Monti, Stefano 2; Varelas, Xaralabos 1
	2018-06
发表期刊	EMBO REPORTS (IF:6.5[JCR-2023],8.3[5-Year])
ISSN	1469-221X
卷号	19 期号:6
发表状态	已发表
DOI	10.15252/embr.201643577
摘要	The transcriptional regulators TAZ and YAP (TAZ/YAP) have emerged as pro-tumorigenic factors that drive many oncogenic traits, including induction of cell growth, resistance to cell death, and activation of processes that promote migration and invasion. Here, we report that TAZ/YAP reprogram cellular energetics to promote the dependence of breast cancer cell growth on exogenous glutamine. Rescue experiments with glutamine-derived metabolites suggest an essential role for glutamate and -ketoglutarate (AKG) in TAZ/YAP-driven cell growth in the absence of glutamine. Analysis of enzymes that mediate the conversion of glutamate to AKG shows that TAZ/YAP induce glutamic-oxaloacetic transaminase (GOT1) and phosphoserine aminotransferase (PSAT1) expression and that TAZ/YAP activity positively correlates with transaminase expression in breast cancer patients. Notably, we find that the transaminase inhibitor aminooxyacetate (AOA) represses cell growth in a TAZ/YAP-dependent manner, identifying transamination as a potential vulnerable metabolic requirement for TAZ/YAP-driven breast cancer.
关键词	breast cancer cellular metabolism glutamine Hippo Transaminase
收录类别	SCI ; SCIE
语种	英语
资助项目	NIH National Heart Lung and Blood Institute[R01HL124392]
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
WOS类目	Biochemistry & Molecular Biology ; Cell Biology
WOS记录号	WOS:000434352400001
出版者	WILEY
WOS关键词	BREAST-CANCER ; HIPPO PATHWAY ; TGF-BETA ; YAP ; GROWTH ; TAZ ; MYC ; INHIBITION ; BIOLOGY ; YAP/TAZ
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/23061
专题	生命科学与技术学院_PI研究组_张力烨组
通讯作者	Varelas, Xaralabos
作者单位	1.Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA 2.Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, Boston, MA 02118 USA 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Yang, Chih-Sheng,Stampouloglou, Eleni,Kingston, Nathan M.,et al. Glutamine-utilizing transaminases are a metabolic vulnerability of TAZ/YAP-activated cancer cells[J]. EMBO REPORTS,2018,19(6).
APA	Yang, Chih-Sheng,Stampouloglou, Eleni,Kingston, Nathan M.,Zhang, Liye,Monti, Stefano,&Varelas, Xaralabos.(2018).Glutamine-utilizing transaminases are a metabolic vulnerability of TAZ/YAP-activated cancer cells.EMBO REPORTS,19(6).
MLA	Yang, Chih-Sheng,et al."Glutamine-utilizing transaminases are a metabolic vulnerability of TAZ/YAP-activated cancer cells".EMBO REPORTS 19.6(2018).