CFTR promotes malignant glioma development via up-regulation of Akt/Bcl2-mediated anti-apoptosis pathway.

CFTR promotes malignant glioma development via up-regulation of Akt/Bcl2-mediated anti-apoptosis pathway. J Cell Mol Med. 2020 May 28;: Authors: Zhao M, Zhang J, Huang W, Dong J, Guo J, U KP, Weng Z, Liu S, Chan HC, Feng H, Jiang X Abstract Cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated Cl- channel, is extensively expressed in the epithelial cells of various tissues and organs. Accumulating evidence indicates that aberrant expression or mutation of CFTR is related to carcinoma development. Malignant gliomas are the most common and aggressive intracranial tumours; however, the role of CFTR in the development of malignant gliomas is unclear. Here, we report that CFTR is expressed in malignant glioma cell lines. Suppression of CFTR channel function or knockdown of CFTR suppresses glioma cell viability whereas overexpression of CFTR promotes it. Additionally, overexpression of CFTR suppresses apoptosis and promotes glioma progression in both subcutaneous and orthotopic xenograft models. Cystic fibrosis transmembrane conductance regulator activates Akt/Bcl2 pathway, and suppression of PI3K/Akt pathway abolishes CFTR overexpression-induced up-regulation of Bcl2 (MK-2206 and LY294002) and cell viability (MK-2206). More importantly, the protein expression level of CFTR is significantly increased in glioblastoma patient samples. Altogether, our study has revealed a mechanism by which CFTR promotes glioma progress...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research