Adenylate kinase hCINAP determines self-renewal of colorectal cancer   stem cells by facilitating LDHA phosphorylation

doi:10.1038/ncomms15308

CORC > 北京大学 > 生命科学学院

	Adenylate kinase hCINAP determines self-renewal of colorectal cancer stem cells by facilitating LDHA phosphorylation
	Ji, Yapeng ; Yang, Chuanzhen ; Tang, Zefang ; Yang, Yongfeng ; Tian, Yonglu ; Yao, Hongwei ; Zhu, Xi ; Zhang, Zeming ; Ji, Jiafu ; Zheng, Xiaofeng
刊名	NATURE COMMUNICATIONS
	2017
关键词	PHENOTYPIC CHARACTERIZATION OXIDATIVE-PHOSPHORYLATION TUMOR-GROWTH METABOLISM METASTASIS TUMORIGENESIS TRANSITIONS PROGRESSION CARCINOMA SURVIVAL
DOI	10.1038/ncomms15308
英文摘要	Targeting the specific metabolic phenotypes of colorectal cancer stem cells (CRCSCs) is an innovative therapeutic strategy for colorectal cancer (CRC) patients with poor prognosis and relapse. However, the context-dependent metabolic traits of CRCSCs remain poorly elucidated. Here we report that adenylate kinase hCINAP is overexpressed in CRC tissues. Depletion of hCINAP inhibits invasion, self-renewal, tumorigenesis and chemoresistance of CRCSCs with a loss of mesenchymal signature. Mechanistically, hCINAP binds to the C-terminal domain of LDHA, the key regulator of glycolysis, and depends on its adenylate kinase activity to promote LDHA phosphorylation at tyrosine 10, resulting in the hyperactive Warburg effect and the lower cellular ROS level and conferring metabolic advantage to CRCSC invasion. Moreover, hCINAP expression is positively correlated with the level of Y10-phosphorylated LDHA in CRC patients. This study identifies hCINAP as a potent modulator of metabolic reprogramming in CRCSCs and a promising drug target for CRC invasion and metastasis.; National Key Research and Development Program of China [2016YFC1302401]; National Science Foundation of China [31670786, 31470754]; Doctoral Fund of the Ministry of Education of China [20130001130003]; SCI(E); ARTICLE; 8
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/473374]
专题	生命科学学院
推荐引用方式 GB/T 7714	Ji, Yapeng,Yang, Chuanzhen,Tang, Zefang,et al. Adenylate kinase hCINAP determines self-renewal of colorectal cancer stem cells by facilitating LDHA phosphorylation[J]. NATURE COMMUNICATIONS,2017.
APA	Ji, Yapeng.,Yang, Chuanzhen.,Tang, Zefang.,Yang, Yongfeng.,Tian, Yonglu.,...&Zheng, Xiaofeng.(2017).Adenylate kinase hCINAP determines self-renewal of colorectal cancer stem cells by facilitating LDHA phosphorylation.NATURE COMMUNICATIONS.
MLA	Ji, Yapeng,et al."Adenylate kinase hCINAP determines self-renewal of colorectal cancer stem cells by facilitating LDHA phosphorylation".NATURE COMMUNICATIONS (2017).