Cilia loss sensitizes cells to transformation by activating the mevalonate pathway

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 transfo...

Full description

Saved in:

Bibliographic Details
Published in:	The Journal of experimental medicine 2018-01, Vol.215 (1), p.177-195
Main Authors:	Deng, Yue-Zhen, Cai, Zhen, Shi, Shuo, Jiang, Hao, Shang, Yu-Rong, Ma, Ning, Wang, Jing-Jing, Guan, Dong-Xian, Chen, Tian-Wei, Rong, Ye-Fei, Qian, Zhen-Yu, Zhang, Er-Bin, Feng, Dan, Zhou, Quan-Li, Du, Yi-Nan, Liu, Dong-Ping, Huang, Xing-Xu, Liu, Lu-Ming, Chin, Eugene, Li, Dang-Sheng, Wang, Xiao-Fan, Zhang, Xue-Li, Xie, Dong
Format:	Article
Language:	eng
Subjects:	Adenocarcinoma Animals Cancer Carcinoma, Pancreatic Ductal - etiology Carcinoma, Pancreatic Ductal - metabolism Carcinoma, Pancreatic Ductal - pathology Cell Line, Tumor Cell Transformation, Neoplastic - genetics Cell Transformation, Neoplastic - metabolism Cilia Cilia - pathology Gene Expression Profiling Humans Inhibitors Lymphocytes T Male Metabolic Networks and Pathways Mevalonic acid Mevalonic Acid - metabolism Mice NIH 3T3 Cells Oncogenes Pancreatic cancer Pancreatic Neoplasms Pancreatic Neoplasms - etiology Pancreatic Neoplasms - metabolism Pancreatic Neoplasms - pathology Regulatory sequences Signal transduction Signaling Statins Sterol Regulatory Element Binding Protein 2 TCF Transcription Factors - metabolism Tissues Transformation Tumorigenesis β-catenin
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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 β catenin-T cell factor (TCF) signaling, which synchronized with sterol regulatory element binding transcription factor 2 (SREBP2), and the regulation of MVA by β-catenin-TCF signaling was recapitulated in a mouse model of pancreatic ductal adenocarcinoma (PDAC) and human PDAC samples. Moreover, disruption of ciliogenesis by depleting dramatically promoted tumorigenesis in the PDAC mouse model, driven by , 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.
ISSN:	0022-1007 1540-9538