6662

SOX9

SOX9 gene encodes a transcription factor essential for a central role in the development and differentiation of multiple cell lineages, such as in neurogenesis, neural crest development, etc. Recent study reported that overexpression of SOX9 mRNA is closely associated with poor clinical outcome of patients with malignant gliomas. In the present study, we have explored the regulatory role of SOX9 in glioma metastasis. To investigate the role of SOX9 in glioma metastasis, SOX9 overexpressed in human glioma cell line U251 on cell migration and invasion was evaluated via wound scratch, Transwell assay without or with Matrigel. SOX9-induced changes in EMT process were evaluated by Western blot. Furthermore, the role of beta-catenin in the regulatory effect of SOX9 on cell migration and invasion, and EMT process was explored by suppressing beta-catenin expression in SOX9-overexpressed U251 cells. SOX9 overexpression in U251 cells resulted in a significant increase in cell migration and invasion. SOX9 overexpression also markedly promoted the EMT process. More importantly, our results revealed that SOX9 stimulated metastasis through activating Wnt/beta-catenin signaling. In summary, this study indicated that the promoting effect of SOX9 on glioma metastasis was, at least in part, through Wnt/beta-catenin signaling. The findings in this study highlight the effectiveness and therapeutic potential to utilize SOX9 targeted strategies in the treatment of glioma.

BACKGROUND: Intrahepatic cholangiocarcinomas develop through a multi-step carcinogenesis. Precancerous lesions are defined as biliary intraepithelial neoplasia. Sex determining region Y-box9 (Sox9) is required for the normal differentiation of the biliary tract. AIMS: To evaluate the Sox9 expression in carcinogenesis and its correlation with clinicopathological features in intrahepatic cholangiocarcinoma. METHODS: Sox9 expression in normal epithelium, biliary intraepithelial neoplasia, and intrahepatic cholangiocarcinoma were investigated immunohistochemically using 43 specimens of intrahepatic cholangiocarcinoma. Sox9 expression in intrahepatic cholangiocarcinoma was compared with the clinicopathological features. The molecular effects of Sox9 were investigated by gene transfection to intrahepatic cholangiocarcinoma cell lines. RESULTS: Sox9 expression was decreased from the normal epithelium to the biliary intraepithelial neoplasia in a stepwise fashion. In 51.2% (22/43) of the patients with intrahepatic cholangiocarcinoma, Sox9 expression was positive, and Sox9 expression was significantly associated with the biliary infiltration (P=0.034) and poor overall survival (P=0.039). Upregulation of Sox9 promoted the cell migration and invasion, and decreased the E-cadherin expression and increased the vimentin and alpha-SMA expression in cell lines. CONCLUSIONS: Decreased Sox9 expression may be related to the early stage of the carcinogenesis of intrahepatic cholangiocarcinoma. Sox9 overexpression in intrahepatic cholangiocarcinoma is related to biliary infiltration and poorer prognosis, and it promotes cell migration and invasion, via the epithelial-to-mesenchymal transition.CI - Copyright (c) 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Sex-determining region Y (SRY)-box 9 (SOX9) is a member of the SOX transcription factor family. Increasing evidence has reported that SOX9 plays different roles in various types of malignancies. However, the role of SOX9 in papillary thyroid cancer (PTC) is still unclear. The aim of this study was to investigate the role of SOX9 in PTC. Our results showed that SOX9 was upregulated in PTC tissues and cell lines. In addition, knockdown of SOX9 significantly inhibited PTC proliferation, colony formation, migration, and invasion, as well as epithelial-mesenchymal transition (EMT) phenotype in TPC-1 and BCPAP cells. Moreover, knockdown of SOX9 significantly inhibited the expression levels of beta-catenin, cyclin D1, and c-Myc in PTC cells. In conclusion, this is the first report demonstrating that knockdown of SOX9 inhibited PTC cell proliferation, invasion, and the EMT process via suppressing Wnt/beta-catenin signaling pathway. Thus, SOX9 may act as a novel molecular target for the prevention and treatment of PTC.

epithelial-mesenchymal transformation is a critical developmental process reiterated in multiple organs throughout embryogenesis. Formation of endocardial cushions, primordia of valves and septa, is a classic example of epithelial-mesenchymal transformation. Several gene mutations are known to affect cardiac valve formation. Sox9 is activated when endocardial endothelial cells undergo mesenchymal transformation and migrate into an extracellular matrix, called cardiac jelly, to form endocardial cushions. In Sox9-null mutants, endocardial cushions are markedly hypoplastic. In these mutants, Nfatc1 is ectopically expressed and no longer restricted to endothelial cells. Further, Sox9-deficient endocardial mesenchymal cells fail to express ErbB3, which is required for endocardial cushion cell differentiation and proliferation. Our results reveal a succession of molecular steps in the pathway of endocardial cushion development. We propose that loss of Sox9 inhibits epithelial-mesenchymal transformation after delamination and initial migration, but before definitive mesenchymal transformation.