OncoTargets and Therapy (Nov 2019)
P120-Catenin And Its Phosphorylation On Tyr228 Inhibits Proliferation And Invasion In Colon Adenocarcinoma Cells
Abstract
Xiuming Ding,1 Xiuqin Wang,2 Shifen Lu,3 Xuemei Gao,4 Shumei Ju4 1Department of Intervention, Linyi Central Hospital, Linyi, People’s Republic of China; 2Department of Dermatology, The Third People’s Hospital of Linyi, Linyi, People’s Republic of China; 3Department of Gynaecology and Obstetrics, The Third People’s Hospital of Linyi, Linyi, People’s Republic of China; 4Department of Paediatrics, Linyi Central Hospital, Linyi, People’s Republic of ChinaCorrespondence: Shumei JuDepartment of Paediatrics, Linyi Central Hospital, No.17, Health Road, Yishui County, Linyi City, Shandong Province 276400, People’s Republic of ChinaEmail [email protected]: 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.Keywords: colon adenocarcinoma, p120-catenin, phosphorylation, prognosis, RhoA
