Feng Jiali, Xu Jie, Xu Ying, Xiong Jun, Xiao Tingting, Jiang Chao, Li Xian, Wang Qian, Li Jie, Li Yong
College of Stomatology, Chongqing Medical University Chongqing, China.
Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences Chongqing, China.
Am J Transl Res. 2019 Feb 15;11(2):557-571. eCollection 2019.
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 ITGαv, ITGβ1, p-ERK, vimentin, MMP2 and MMP9, and increased the levels of p-p38, E-cadherin, caspase3 and caspase9. CLIC1 overexpression enhanced the ITGαv, ITGβ1, 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 ITGαv and ITGβ1, which led to activation of the MAPK/ERK and MAPK/p38 signal pathways.
氯离子细胞内通道蛋白1（CLIC1）是氯离子通道蛋白家族的成员之一，在许多恶性肿瘤中发挥着促进作用，但其在口腔癌中的作用仍不清楚。因此，本研究旨在探讨CLIC1对口腔癌细胞体外增殖的影响，并评估其在细胞增殖、凋亡、迁移、侵袭、血管生成以及对顺铂的化疗敏感性和可能的信号通路中的作用。结果表明，CLIC1缺失可抑制口腔鳞状细胞癌（OSCC）细胞的体外增殖、侵袭、迁移和血管生成，但可促进细胞凋亡并增加对顺铂的药物敏感性。相反，CLIC1上调与细胞增殖、侵袭、迁移和血管生成呈正相关。机制上，CLIC1沉默降低了ITGαv、ITGβ1、p-ERK、波形蛋白、MMP2和MMP9的水平，并增加了p-p38、E-钙黏蛋白、caspase3和caspase9的水平。CLIC1过表达增强了ITGαv、ITGβ1、p-ERK、波形蛋白、MMP2和MMP9的水平，并降低了E-钙黏蛋白的表达。总体而言，这些结果表明CLIC1促进了OSCC的进展，我们推测其潜在机制可能与ITGαv和ITGβ1的调节有关，从而导致MAPK/ERK和MAPK/p38信号通路的激活。
