SCRIB Is Involved in the Progression of Ovarian Carcinomas in Association with the Factors Linked to Epithelial-to-Mesenchymal Transition and Predicts Shorter Survival of Diagnosed Patients.

Usama Khamis Hussein,Kyoung Min Kim,Ho Sung Park,Myoung Ja Chung,Woo Sung Moon,See-Hyoung Park,Dong Hyu Cho,Myoung Jae Kang,Won Ku Choi,Asmaa Gamal Ahmed,Ho Lee,Kyu Yun Jang,Sang Jae Noh

doi:10.3390/biom11030405

Abstract

SCRIB is a polarity protein important in maintaining cell junctions. However, recent reports have raised the possibility that SCRIB might have a role in human cancers. Thus, this study evaluated the roles of SCRIB in ovarian cancers. In 102 human ovarian carcinomas, nuclear expression of SCRIB predicted shorter survival of ovarian carcinoma patients, especially in the patients who received post-operative chemotherapy. In SKOV3 and SNU119 ovarian cancer cells, overexpression of SCRIB stimulated the proliferation and invasion of cells. Knockout of SCRIB inhibited in vivo tumor growth of SKOV3 cells and overexpression of SCRIB promoted tumor growth. Overexpression of SCRIB stimulated epithelial-to-mesenchymal transition by increasing the expression of N-cadherin, snail, TGF-β1, and smad2/3, and decreasing the expression of E-cadherin; the converse was observed with inhibition of SCRIB. In conclusion, this study presents the nuclear expression of SCRIB as a prognostic marker of ovarian carcinomas and suggests that SCRIB is involved in the progression of ovarian carcinomas by stimulating proliferation and epithelial-to-mesenchymal transition-related invasiveness.

Highlights

The Expression of SCRIB Is Associated with the Progression of Ovarian Carcinomas
NSCRIB positivity predicted shorter overall survival (OS) of high-grade serous carcinoma (HGSC), the most common histologic type of ovarian cancer with a relatively unfavorable prognosis. These findings suggest that SCRIB is involved in the progression of ovarian carcinomas and might be used as a prognostic marker of ovarian carcinoma patients
We demonstrated that SCRIB stimulates proliferation and invasiveness of ovarian cancer cells in conjunction with activation of the factors linked to the epithelial-to-mesenchymal transition (EMT)

Summary

Introduction

SCRIB (scribble) is a protein important in maintaining cell polarity and tight junctions of epithelial cells [1]. The role of SCRIB as a component of cell junctions suggests that. SCRIB acts as a tumor suppressor because structural and functional alteration of cell polarity induces tumorigenesis [2,3]. Loss of SCRIB can induce mammary tumorigenesis and promote prostate neoplasia [4,5]. The tumor-suppressive role of SCRIB is supported by a report that the loss of SCRIB causes loosening of the cell to cell contact and leading epithelial-to-mesenchymal transition (EMT) [1]. Mislocalization of SCRIB from the cytoplasmic membrane to the cytoplasm or nuclei was presented as a tumorigenic phenotype of SCRIB [4,6]

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Discussion

Conclusion