Department of Surgery and Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, 930-0194, Japan.
Department of Pharmaceutical Physiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
J Physiol Sci. 2020 Feb 17;70(1):15. doi: 10.1186/s12576-020-00740-7.
Pathophysiological functions of chloride intracellular channel protein 3 (CLIC3) in human gastric cancer have been unclear. In the tissue microarray analysis using 107 gastric cancer specimens, CLIC3 expression was negatively correlated with pathological tumor depth, and the patients with lower expression of CLIC3 exhibited poorer prognosis. CLIC3 was expressed in the plasma membrane of cancer cells in the tissue. CLIC3 expression was also found in a human gastric cancer cell line (MKN7). In whole-cell patch-clamp recordings of the cells expressing CLIC3, NPPB-sensitive outwardly rectifying Cl currents were observed. Cell proliferation was significantly accelerated by knockdown of CLIC3 in MKN7 cells. On the other hand, the proliferation was attenuated by exogenous CLIC3 expression in human gastric cancer cells (KATOIII and NUGC-4) in which endogenous CLIC3 expression is negligible. Our results suggest that CLIC3 functions as a Cl channel in the plasma membrane of gastric cancer cells and that decreased expression of CLIC3 results in unfavorable prognosis of gastric cancer patients.
氯离子通道蛋白 3（CLIC3）在人类胃癌中的病理生理功能尚不清楚。在使用 107 个胃癌标本的组织微阵列分析中，CLIC3 的表达与病理肿瘤深度呈负相关，CLIC3 表达较低的患者预后较差。CLIC3 表达在组织中癌细胞的质膜上。在人胃癌细胞系（MKN7）中也发现了 CLIC3 的表达。在表达 CLIC3 的细胞的全细胞膜片钳记录中，观察到 NPPB 敏感的外向整流 Cl 电流。在 MKN7 细胞中敲低 CLIC3 可显著加速细胞增殖。另一方面，在胃癌细胞（KATOIII 和 NUGC-4）中，外源性 CLIC3 表达可减弱，而这些细胞中内源性 CLIC3 表达可忽略不计。我们的结果表明，CLIC3 在胃癌细胞质膜中作为 Cl 通道发挥作用，CLIC3 表达降低导致胃癌患者预后不良。
