Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is expressed in the epithelial cells of a wide range of organs/tissues from which most cancers are derived.
Although accumulating reports have indicated the association of cancer incidence with genetic variations in CFTR gene, the exact role of CFTR in cancer development and the possible underlying mechanism have not been elucidated. Here, we report that CFTR expression is significantly decreased in both prostate cancer cell lines and human prostate cancer tissue samples. Overexpression of CFTR in prostate cancer cell lines suppresses tumor progression (cell growth, adhesion and migration), whereas knockdown of CFTR leads to enhanced malignancies both in vitro and in vivo. In addition, we demonstrate that CFTR knockdown-enhanced cell proliferation, cell invasion and migration are significantly reversed by antibodies against either urokinase plasminogen activator (uPA) or uPA receptor (uPAR), which are known to be involved in various malignant traits of cancer development. More interestingly, overexpression of CFTR suppresses uPA by upregulating the recently described tumor suppressor microRNA-193b (miR-193b), and overexpression of pre-miR-193b significantly reverses CFTR knockdown-enhanced malignant phenotype and abrogates elevated uPA activity in prostate cancer cell line. Finally, we show that CFTR gene transfer results in significant tumor repression in prostate cancer xenografts in vivo. Taken together, the present study has demonstrated a previously undefined tumor-suppressing role of CFTR and its involvement in regulation of miR-193b in prostate cancer development.
Written by:
Xie C, Jiang XH, Zhang JT, Sun TT, Dong JD, Sanders AJ, Diao RY, Wang Y, Fok KL, Tsang LL, Yu MK, Zhang XH, Chung YW, Ye L, Zhao MY, Guo JH, Xiao ZJ, Lan HY, Ng CF, Lau KM, Cai ZM, Jiang WG, Chan HC. Are you the author?
Epithelial Cell Biology Research Center, School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong.
Reference: Oncogene. 2012 Jul 16. Epub ahead of print.
doi: 10.1038/onc.2012.251
PubMed Abstract
PMID: 22797075
UroToday.com Investigative Urology Section
