Inhibition of ClC-5 suppresses proliferation and induces apoptosis in cholangiocarcinoma cells through the Wnt/β-catenin signaling pathway
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Chloride channel-5 (ClC-5), an important branch of the ClCfamily, is involved in the regulation of the proliferation andcell-fate of a variety of cells, including tumor cells. However,its function in cholangiocarcinoma (CCA) cells remains enigmatic. Here, we discovered that ClC-5 was up-regulated in CCAtissues and CCA cell lines, while ClC-5 silencing inhibited CCAcell proliferation and induced apoptosis. Further mechanismstudies revealed that ClC-5 inhibition could inhibit Wnt/β-cateninsignaling activity and further activate the mitochondria apoptoticpathway in CCA cells. Furthermore, rescuing Wnt/β-catenin signalingactivation eliminated the anti-tumor function of ClC-5knockdown. Together, our research findings illustrated that ClC-5inhibition plays an anti-tumor role in CCA cells via inhibitingthe activity of the Wnt/β-catenin pathway, which in turn activatesthe mitochondrial apoptotic pathway.
Abstract
Chloride channel-5 (ClC-5), an important branch of the ClCfamily, is involved in the regulation of the proliferation andcell-fate of a variety of cells, including tumor cells. However,its function in cholangiocarcinoma (CCA) cells remains enigmatic. Here, we discovered that ClC-5 was up-regulated in CCAtissues and CCA cell lines, while ClC-5 silencing inhibited CCAcell proliferation and induced apoptosis. Further mechanismstudies revealed that ClC-5 inhibition could inhibit Wnt/β-cateninsignaling activity and further activate the mitochondria apoptoticpathway in CCA cells. Furthermore, rescuing Wnt/β-catenin signalingactivation eliminated the anti-tumor function of ClC-5knockdown. Together, our research findings illustrated that ClC-5inhibition plays an anti-tumor role in CCA cells via inhibitingthe activity of the Wnt/β-catenin pathway, which in turn activatesthe mitochondrial apoptotic pathway.
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