Cilia loss sensitizes cells to transformation by activating the mevalonate pathway

doi:10.1084/jem.20170399

	Cilia loss sensitizes cells to transformation by activating the mevalonate pathway
	Deng, Yue-Zhen 1,4; Cai, Zhen 1; Shi, Shuo 1; Jiang, Hao 1; Shang, Yu-Rong 1; Ma, Ning 1; Wang, Jing-Jing 1; Guan, Dong-Xian 1; Chen, Tian-Wei 1; Rong, Ye-Fei 5; Qian, Zhen-Yu 1; Zhang, Er-Bin 1; Feng, Dan 1; Zhou, Quan-Li 3; Du, Yi-Nan 7; Liu, Dong-Ping 1; Huang, Xing-Xu ; Liu, Lu-Ming 6; Chin, Eugene 3; Li, Dang-Sheng 2; Wang, Xiao-Fan 8; Zhang, Xue-Li 9; Xie, Dong1
	2018-01
发表期刊	JOURNAL OF EXPERIMENTAL MEDICINE
ISSN	0022-1007
卷号	215 期号:1 页码:177-195
发表状态	已发表
DOI	10.1084/jem.20170399
摘要	Although cilia loss and cell transformation are frequently observed in the early stage of tumorigenesis, the roles of cilia in cell transformation are unknown. In this study, disrupted ciliogenesis was observed in cancer cells and pancreatic cancer tissues, which facilitated oncogene-induced transformation of normal pancreatic cells (HPDE6C7) and NIH3T3 cells through activating the mevalonate (MVA) pathway. Disruption of ciliogenesis up-regulated MVA enzymes through beta-catenin-T cell factor (TCF) signaling, which synchronized with sterol regulatory element binding transcription factor 2 (SREBP2), and the regulation of MVA by beta-catenin-TCF signaling was recapitulated in a mouse model of pancreatic ductal adenocarcinoma (PDAC) and human PDAC samples. Moreover, disruption of ciliogenesis by depleting Tg737 dramatically promoted tumorigenesis in the PDAC mouse model, driven by Kras(G12D), which was inhibited by statin, an inhibitor of the MVA pathway. Collectively, this study emphasizes the crucial roles of cilia in governing the early steps of the transformation by activating the MVA pathway, suggesting that statin has therapeutic potential for pancreatic cancer treatment.
收录类别	SCI ; SCIE
语种	英语
资助项目	Shanghai Institutes for Biological Science[2014KIP105]
WOS研究方向	Immunology ; Research & Experimental Medicine
WOS类目	Immunology ; Medicine, Research & Experimental
WOS记录号	WOS:000419134400015
出版者	ROCKEFELLER UNIV PRESS
WOS关键词	PANCREATIC-CANCER ; STATIN THERAPY ; METABOLISM ; AUTOPHAGY ; PROLIFERATION ; INHIBITION ; REDUCTASE ; COENZYME
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/16288
专题	生命科学与技术学院_特聘教授组_谢东组
通讯作者	Zhang, Xue-Li; Xie, Dong
作者单位	1.Chinese Acad Sci, Inst Nutr Sci, Key Lab Nutr & Metab, Shanghai, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Biochem & Cell Biol, Shanghai, Peoples R China 3.Shanghai Jiao Tong Univ, Chinese Acad Sci, Sch Med, Inst Hlth Sci,Shanghai Inst Biol Sci, Shanghai, Peoples R China 4.Cent S Univ, Xiangya Hosp, Ctr Mol Med, Changsha, Hunan, Peoples R China 5.Fudan Univ, Zhongshan Hosp, Gen Surg Dept, Pancreat Canc Grp, Shanghai, Peoples R China 6.Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai, Peoples R China 7.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 8.Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC USA 9.Southern Med Univ, Dept Gen Surg, Fengxian Hosp, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Deng, Yue-Zhen,Cai, Zhen,Shi, Shuo,et al. Cilia loss sensitizes cells to transformation by activating the mevalonate pathway[J]. JOURNAL OF EXPERIMENTAL MEDICINE,2018,215(1):177-195.
APA	Deng, Yue-Zhen.,Cai, Zhen.,Shi, Shuo.,Jiang, Hao.,Shang, Yu-Rong.,...&Xie, Dong.(2018).Cilia loss sensitizes cells to transformation by activating the mevalonate pathway.JOURNAL OF EXPERIMENTAL MEDICINE,215(1),177-195.
MLA	Deng, Yue-Zhen,et al."Cilia loss sensitizes cells to transformation by activating the mevalonate pathway".JOURNAL OF EXPERIMENTAL MEDICINE 215.1(2018):177-195.