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

Biomolecules. 2021 Mar 9;11(3):405. 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.

Keywords: SCRIB; cancer; epithelial-to-mesenchymal transition; ovary; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • Chemotherapy, Adjuvant
  • Disease Progression*
  • Epithelial-Mesenchymal Transition*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Nude
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Proportional Hazards Models
  • Survival Analysis
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Membrane Proteins
  • SCRIB protein, human
  • Tumor Suppressor Proteins