Cilia loss sensitizes cells to transformation by activating the mevalonate pathway

• DOI: 10.1084/jem.20170399
• Publication Date: 2017-12-13T14:45:13Z
• Authors: Yue-Zhen Deng; Zhen Cai; Shuo Shi; Hao Jiang; Yu-Rong Shang; Ning Ma; Jing-Jing Wang; Dong-Xian Guan; Tian-Wei Chen; Ye-Fei Rong; Zhen-Yu Qian; Er-Bin Zhang; Dan Feng; Quan-Li Zhou; Yi-Nan Du; Dong-Ping Liu; Xing-Xu Huang; Lu-Ming Liu; Eugene Chin; Dang-Sheng Li; Xiao-Fan Wang; Xue-Li Zhang; Dong Xie
• Keywords: Ciliogenesis

Although cilia loss and cell transformation are frequently observed in the early stage of tumorigenesis, roles unknown. In this study, disrupted ciliogenesis was cancer cells pancreatic tissues, which facilitated oncogene-induced normal (HPDE6C7) NIH3T3 through activating mevalonate (MVA) pathway. Disruption up-regulated MVA enzymes β catenin-T factor (TCF) signaling, synchronized with sterol regulatory element binding transcription 2 (SREBP2), regulation by β-catenin-TCF signaling recapitulated a mouse model ductal adenocarcinoma (PDAC) human PDAC samples. Moreover, disruption depleting Tg737 dramatically promoted tumorigenesis model, driven KrasG12D , inhibited statin, an inhibitor Collectively, study emphasizes crucial governing steps pathway, suggesting that statin has therapeutic potential for treatment.