CLIC1 promotes the progression of oral squamous cell carcinoma via integrins/ERK pathways.

Chloride intracellular channel 1 (CLIC1), a member of the chloride channel protein family, acts as a promoter in many malignancies, but its role in oral cancer remains unclear. Hence, this research aimed to explore the effects of CLIC1 on the progression of oral cancer cells in vitro, and we assessed its role in cell proliferation, apoptosis, migration, invasion, angiogenesis, and chemosensitivity to cisplatin and possible signaling pathways. The results demonstrated that CLIC1 depletion inhibited the proliferation, invasion, migration and angiogenesis of oral squamous cell carcinoma (OSCC) cells in vitro, but promoted cell apoptosis and increased the drug susceptibility to cisplatin. In contrast, CLIC1 upregulation was positively correlated with cell proliferation, invasion and migration and angiogenesis. Mechanistically, CLIC1 silencing decreased the levels of ITG alpha v, ITG beta 1, p-ERK, vimentin, MMP2 and MMP9, and increased the levels of p-p38, E-cadherin, caspase3 and caspase9. CLIC1 overexpression enhanced the ITG alpha v, ITG beta 1, p-ERK, vimentin, MMP2 and MMP9 levels and decreased E-cadherin expression. Overall, these results indicated that CLIC1 promotes the progression of OSCC, and we speculated that its potential mechanism may be related to the regulation of ITG alpha v and ITG beta 1, which led to activation of the MAPK/ERK and MAPK/p38 signal pathways.