P120-Catenin And Its Phosphorylation On Tyr228 Inhibits Proliferation And Invasion In Colon Adenocarcinoma Cells
P120-Catenin And Its Phosphorylation On Tyr228 Inhibits Proliferation And Invasion In Colon Adenocarcinoma Cells
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DOI：
10.2147/ott.s211973
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发表时间：
2019-01-01
影响因子：
4
通讯作者：
Ju, Shumei
中科院分区：
文献类型：
--
作者：
Ding, Xiuming;Wang, Xiuqin;Ju, Shumei
背景：结直肠癌是世界范围内第三大常见恶性肿瘤，是癌症相关死亡的主要原因之一。P120-catenin蛋白在多种恶性疾病中发挥抗癌作用。本研究旨在探讨p120-catenin磷酸化在结肠腺癌（CAC）中的表达及其与预后的关系，以及p120-catenin在肿瘤进展中的作用。通过使用Lipofectamine 3000瞬时转染到SW 480细胞中实现过表达和敲低。CCK-8法和Matrigel-transwell法分别检测细胞增殖和侵袭能力。进行RT-qPCR和Western印迹以分析下游信号传导途径。采用卡方检验分析p120-catenin与临床病理特征的相关性。结果：p120-catenin和pY 228-p120-catenin在CAC组织中的表达水平较低，且与肿瘤的临床分期有关。此外，pY 228-p120-catenin表达水平较低提示CAC患者预后较差，而p120-catenin表达水平与CAC患者预后无显著性差异。p120-catenin过表达可通过稳定E-cadherin和抑制RhoA活化抑制SW 480细胞增殖和侵袭。结论：P120-catenin及其Y228位点的磷酸化通过多种信号通路参与结肠腺癌的抗肿瘤作用。肿瘤组织中p120-catenin上Y228的低磷酸化表明结肠腺癌患者的临床结局较差。
Background: Colorectal cancer is the third most common malignancy worldwide and is one of the leading causes of cancer-related mortality. P120-catenin protein has been well known to exert anticancer effects in several malignant diseases. The aim of our study was to investigate the phosphorylation of p120-catenin in colon adenocarcinoma (CAC) and its association with prognosis, and its role in tumor progression.Methods: Immunohistochemical (IHC) staining was used to explore the existence of p120-catenin and its phosphorylation on tyrosine 228 (pY228-p120-catenin) in CAC samples. Overexpression and knockdown were achieved by transient transfection into SW480 cells using Lipofectamine 3000. CCK-8 and Matrigel-transwell assays were conducted to evaluate proliferation and invasion capacities, respectively. RT-qPCR and Western blotting were performed to analyze downstream signaling pathways. Chi-square test was used to analyze correlations between p120-catenin and clinicopathological characteristics. Univariate and multivariate analyses were used to identify independent prognostic factors.Results: Lower p120-catenin and pY228-p120-catenin levels were identified in CAC tissues and were both correlated with advanced tumor stage. Additionally, lower pY228-p120catenin indicated poorer prognosis of CAC patients although p120-catenin showed little significance. Overexpression of p120-catenin suppressed SW480 cell proliferation and invasion via stabilizing E-cadherin and inhibiting RhoA activation. Phosphorylation of Y228 on p120-catenin by Src protein enhanced the anticancer effects of p120-catenin.Conclusion: P120-catenin and its phosphorylation on site Y228 play anticancer effects in colon adenocarcinoma via multiple signaling pathways. Hypophosphorylation of Y228 on p120-catenin in tumor tissues indicates poor clinical outcomes of colon adenocarcinoma patients.