CFTR inhibits the invasion and growth of esophageal cancer cells by inhibiting the expression of NF‐κB

Abstract

Our study aimed to explore the function of cystic fibrosis transmembrane conductance regulator (CFTR) in esophageal cancer. Twenty patients with esophageal squamous cell carcinoma (ESCC) and 20 patients with esophageal adenocarcinoma (EA) were enrolled in this study. The levels of CFTR and NF‐κB in tumor tissues and adjacent normal tissues were detected, respectively. The expression of CFTR were detected by qRT‐PCR and Western blot in normal esophageal cell line, esophagus squamous cell, carcinoma cell lines, and EA cell lines, respectively. Effects of CFTR silencing and overexpression on NF‐κB protein expression were detected by Western blot. Transwell assay was performed to detect cell invasion. Mouse tumor model was established and the effect of CFTR inhibitor on tumor growth was examined. The expression of CFTR was downregulated in tumor tissues and cancer cell lines. CFTR silencing promoted the expression of NF‐κB‐p65 and NF‐κB‐p50, and the results of CFTR overexpression were reversed. In addition, CFTR silencing promoted the invasion of cancer cells and tumor growth in mice. Besides that, NF‐κB inhibitor reduced the enhancing effects of CFTR silencing on esophageal cell invasion. We conclude that CFTR inhibits the growth and migration of esophageal cancer cells by downregulating of the NF‐κB protein expression.

Epigenetic Modification of CFTR in Head and Neck Cancer

“…Of note, a previous study reported that downregulation of CFTR was associated with a proportional downregulation of E-cadherin and activation of NFκB/uPA, resulting in disruption of cell polarity, induction of epithelial-to-mesenchymal transition (EMT), and invasion in breast cancer [51]. In addition, CFTR was shown to inhibit invasion by suppressing NFκB in esophageal cancer cells [55]. Increasing evidence also points to direct or indirect regulation of cell-to-cell junctions by CFTR [56,57].…”

What Role Does CFTR Play in Development, Differentiation, Regeneration and Cancer?

“…Other mechanisms may also be the cause of CFTR downregulation in cancer, including altered cell signalling or microenvironment changes within tumours. Whatever the cause, CFTR downregulation has been reported in cancer tissues and cells from pancreas [168], prostate [18], breast [18], lung [169,170] and respiratory tract [25], oesophagus [171], colon [24,172] and brain [173]. This downregulation was usually associated with poor prognoses [24,25,169], poor survival rates [172,173] and/or increased malignant behaviours, e.g., metastasis [25,[169][170][171].…”

“…It is also possible that the two mechanisms occur in parallel, rendering CFTR a pleiotropic tumour suppressor. CFTR was also found to inhibit the growth and migration of oesophageal cancer cells by downregulating NF-kB expression [171].…”

Integrated analysis of DNA methylation and mRNA expression profiles to identify key genes in head and neck squamous cell carcinoma

“…Also, further analysis suggested it could be employed as an independent predictor for the prognosis of cancer patients [40]. Cystic fibrosis transmembrane conductance regulator (CFTR), a gene mainly expressed in epithelial cells, was found to play pivotal roles in both physiological processes and pathological stages [41]. Specifically, it was illustrated to mediate the innate immune process, which presents more and more impact on cancer regulation due to the emergence of immunotherapy [42].…”