P120-Catenin And Its Phosphorylation On Tyr228 Inhibits Proliferation And Invasion In Colon Adenocarcinoma Cells.

ABSTRACT: 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-p120-catenin 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.

SUBMITTER: Ding X 

PROVIDER: S-EPMC6884968 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature