Li Tong-Fei, Qin Sheng-Hui, Ruan Xu-Zhi, Wang Xi
Department of Pathology, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Pulmonary Disease of Ministry of Health of China, Wuhan, Hubei 430030, P.R. China.
Oncol Rep. 2015 Nov;34(5):2357-64. doi: 10.3892/or.2015.4226. Epub 2015 Aug 26.
p120-catenin (p120), an E-cadherin regulator, has been implicated as central to a series of genetic and epigenetic changes that ultimately lead to tumor progression and metastasis. Ras-related C3 botulinum toxin substrate 1 (Rac1)and p21-activated kinases (PAKs) are effectors of p120. In the present study, we examined the expression of p120, Rac1 and Pak1 using immunohistochemistry in human gastric cancer tissues. Then, we used the gastric cancer SGC7901 and AGS cell lines to explore the possible mechanism of p120, Rac1 and Pak1 in the progress of gastric cancer. Western blotting was used to detect the expression of p120, Rac1 and Pak1 in the two cell lines. Next, p120 was silenced using p120 siRNA or overexpression of p120 by transfection of the plasmid p120 1A into the two cell types, western blotting was used to investigate the expression changes of Rac1 and Pak1. Furthermore, the effects of p120 siRNA-mediated knockdown or overexpression on the proliferation and invasive ability of gastric cancer cells were investigated using wound healing test and Matrigel invasion assays. The results showed that p120 was downregulated in both poorly differentiated group and well differentiated human gastric cancer. However, Rac1 and Pak1 were upregulated in poorly differentiated tissues and remain low in well differentiated gastric cancer tissues. In the two gastric cancer cell lines, although the expression of Rac1 and Pak1 remained unchanged after the p120 knockdown, the expressions of Rac1 and Pak1 protein were decreased after p120 overexpression in both SGC7901 and AGS cells. Furthermore, knockdown of p120 promoted gastric cancer cell proliferation and invasion; overexpression of p120 reduced the proliferation and invasion of gastric cancer cells. In conclusion, based on our results, we speculate that p120 participates in the progress of gastric cancer through regulating Rac1 and Pak1, which provides a potential prevention and a promising therapeutical approach for the patients with gastric cancer.
p120连环蛋白（p120）是一种E-钙黏蛋白调节因子，被认为是一系列最终导致肿瘤进展和转移的基因和表观遗传变化的核心因素。Ras相关的C3肉毒杆菌毒素底物1（Rac1）和p21激活激酶（PAKs）是p120的效应器。在本研究中，我们使用免疫组织化学方法检测了人胃癌组织中p120、Rac1和Pak1的表达。然后，我们使用胃癌SGC7901和AGS细胞系来探究p120、Rac1和Pak1在胃癌进展中的可能机制。采用蛋白质免疫印迹法检测这两种细胞系中p120、Rac1和Pak1的表达。接下来，使用p120小干扰RNA（siRNA）使p120沉默，或将质粒p120 1A转染到这两种细胞类型中使p120过表达，通过蛋白质免疫印迹法研究Rac1和Pak1的表达变化。此外，使用伤口愈合试验和基质胶侵袭试验研究p120 siRNA介导的敲低或过表达对胃癌细胞增殖和侵袭能力的影响。结果显示，在低分化组和高分化的人胃癌组织中p120均下调。然而，Rac1和Pak1在低分化组织中上调，而在高分化胃癌组织中保持低水平。在这两种胃癌细胞系中，虽然p120敲低后Rac1和Pak1的表达保持不变，但在SGC7901和AGS细胞中p120过表达后，Rac1和Pak1蛋白的表达均降低。此外，p120敲低促进了胃癌细胞的增殖和侵袭；p120过表达则降低了胃癌细胞的增殖和侵袭。总之，基于我们的研究结果，我们推测p120通过调节Rac1和Pak1参与胃癌进展过程，这为胃癌患者提供了一种潜在的预防和有前景的治疗方法。
