Downregulation of CFTR promotes epithelial-to-mesenchymal transition and is associated with poor prognosis of breast cancer

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• 作者：Jie Ting Zhang ; Xiao Hua Jiang ; Chen Xie ; Hong Cheng ; Jian Da Dong ; Yan Wang ; Kin Lam Fok ; Xiao Hu Zhang ; Ting Ting Sun ; Lai Ling Tsang ; Hao Chen ; Xiao Juan Sun ; Yiu Wa Chung ; Zhi Ming Cai ; Wen Guo Jiang ; Hsiao Chang Chan
• 关键词：Epithelial-to-mesenchymal transition (EMT) ; CFTR ; Breast cancer ; Prognosis ; uPA
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Cell Research
• 出版年：December, 2013
• 年：2013
• 卷：1833
• 期：12
• 页码：2961-2969
• 全文大小：1111 K

文摘

The epithelial-to-mesenchymal transition (EMT), a process involving the breakdown of cell-cell junctions and loss of epithelial polarity, is closely related to cancer development and metastatic progression. While the cystic fibrosis transmembrane conductance regulator (CFTR), a Cl^{鈭?/sup> and HCO₃鈭?/sup> conducting anion channel expressed in a wide variety of epithelial cells, has been implicated in the regulation of epithelial polarity, the exact role of CFTR in the pathogenesis of cancer and its possible involvement in EMT process have not been elucidated. Here we report that interfering with CFTR function either by its specific inhibitor or lentiviral miRNA-mediated knockdown mimics TGF-尾₁-induced EMT and enhances cell migration and invasion in MCF-7. Ectopic overexpression of CFTR in a highly metastatic MDA-231 breast cancer cell line downregulates EMT markers and suppresses cell invasion and migration in vitro, as well as metastasis in vivo. The EMT-suppressing effect of CFTR is found to be associated with its ability to inhibit NF魏B targeting urokinase-type plasminogen activator (uPA), known to be involved in the regulation of EMT. More importantly, CFTR expression is found significantly downregulated in primary human breast cancer samples, and is closely associated with poor prognosis in different cohorts of breast cancer patients. Taken together, the present study has demonstrated a previously undefined role of CFTR as an EMT suppressor and its potential as a prognostic indicator in breast cancer.}