%0 Journal Article
%T Cilia loss sensitizes cells to transformation by activating the mevalonate pathway
%A Cai
%A Chen
%A Chin
%A Dan
%A Dan Feng
%A Dang-Sheng
%A Dang-Sheng Li
%A Deng
%A Dong
%A Dong Xie
%A Dong-Ping
%A Dong-Ping Liu
%A Dong-Xian
%A Dong-Xian Guan
%A Du
%A Er-Bin
%A Er-Bin Zhang
%A Eugene
%A Eugene Chin
%A Feng
%A Guan
%A Hao
%A Hao Jiang
%A Huang
%A Jiang
%A Jing-Jing
%A Jing-Jing Wang
%A Li
%A Liu
%A Lu-Ming
%A Lu-Ming Liu
%A Ma
%A Ning
%A Ning Ma
%A Qian
%A Quan-Li
%A Quan-Li Zhou
%A Rong
%A Shang
%A Shi
%A Shuo
%A Shuo Shi
%A Tian-Wei
%A Tian-Wei Chen
%A Wang
%A Xiao-Fan
%A Xiao-Fan Wang
%A Xie
%A Xing-Xu
%A Xing-Xu Huang
%A Xue-Li
%A Xue-Li Zhang
%A Ye-Fei
%A Ye-Fei Rong
%A Yi-Nan
%A Yi-Nan Du
%A Yu-Rong
%A Yu-Rong Shang
%A Yue-Zhen
%A Yue-Zhen Deng
%A Zhang
%A Zhen
%A Zhen Cai
%A Zhen-Yu
%A Zhen-Yu Qian
%A Zhou
%J JEM | The Journal of Experimental Medicine
%D 2018
%R 10.1084/jem.20170399
%X 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 ¦Â catenin¨CT cell factor (TCF) signaling, which synchronized with sterol regulatory element binding transcription factor 2 (SREBP2), and the regulation of MVA by ¦Â-catenin¨CTCF 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 KrasG12D, 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.
%U http://jem.rupress.org/content/215/1/177