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

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.

Individual and Co-Expression Patterns of FAM83H and SCRIB at Diagnosis Are Associated with the Survival of Colorectal Carcinoma Patients

“…In line with our results, a higher expression of SCRIB in human cancers has been reported in CRC [ 20 , 37 ], hepatocellular carcinoma [ 22 ], breast cancer [ 15 ], and prostate cancer [ 15 ]. Furthermore, a higher expression of SCRIB also predicted shorter survival of ovarian carcinoma [ 24 ] and gastric carcinoma [ 7 ]. However, controversially, the expression of SCRIB was decreased compared to normal tissue in oropharyngeal squamous cell carcinoma, breast cancer, uterine cervical cancer, lung cancer, and lymphoma [ 15 , 38 ].…”

“…After that, we used the sum of immunohistochemical staining scores from each core. The final immunohistochemical staining score ranged from zero to sixteen [ 3 , 9 , 24 , 31 ]…”

“…The positivity for the immunohistochemical expression of FAM83H and SCRIB was determined by using a receiver operating characteristic (ROC) curve analysis [ 32 ]. The cut-off point for the immunohistochemical staining score was the point with the highest area under the curve (AUC) to predict the cancer-related deaths of patients [ 6 , 24 , 32 ]. The prognosis of CRC patients was evaluated for cancer-specific survival (CSS) and relapse-free survival (RFS) through September 2021.…”

“…In the liver [ 22 ] and breast [ 23 ], the deregulation of SCRIB promoted tumor formation. In addition, a higher expression of SCRIB was associated with the shorter survival of ovarian and gastric cancer patients [ 7 , 24 ].…”

Afadin couples RAS GTPases to the polarity rheostat Scribble

“…To date, such experiments have provided a complex and inconsistent account of AFDN and SCRIB function. This includes numerous observations of both increased or decreased cellular proliferation, motility or invasion 38,[83][84][85] . This is likely due to both context and cell type dependence as well as the use of RNA-mediated knockdown approaches which typically retain a significant level of protein expression.…”