SOX17 Inhibits Tumor Metastasis Via Wnt Signaling In Endometrial Cancer

• Main Authors: Zhou W, Wang K, Wang J, Qu J, Du G, Zhang Y
• Format: Article
• Language: English
• Published: Dove Medical Press 2019-10-01
• Series: OncoTargets and Therapy
• Subjects: SOX17; endometrial cancer (EC); migration; high-mobility group(HMG)
• Online Access: https://www.dovepress.com/sox17-inhibits-tumor-metastasis-via-wnt-signaling-in-endometrial-cance-peer-reviewed-article-OTT

Weiqiang Zhou, Kai Wang, Jingyun Wang, Junjie Qu, Guiqiang Du, Yongli Zhang Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Yongli ZhangShanghai First Maternity and Infant Hospital, Tongji University School of Medicine, No. 2699 Gaokexi Road, Shanghai 201204, People’s Republic of ChinaTel [phone]Fax [phone]Email [e-mail]: Endometrial cancer (EC) is the most common gynecological malignancy with high incidence of metastasis, while the mechanism of metastasis in EC is not clear.Methods: Immunohistochemistry and real-time PCR assays were used to assess expression of SOX17 in paraffin-embedded tissues from EC patients and in EC cells. The migration of EC cells was assessed by wound-healing and Transwell assays as well as in an in vitro study of nude mice. In addition, the expression of specific proteins was analyzed by Western blot.Results: We observed that SOX17 expression levels were relatively high in stage I EC specimens, and were significantly correlated with the epithelial cadherin (E-cadherin) and β-catenin expression. Additionally, stage II EC patients whose specimens had relatively high SOX17 expression levels had better outcomes. Wound-healing and Transwell assays and in vivo murine experiments revealed that SOX17 inhibited EC cell migration. Meanwhile, SOX17 increased expression of E-cadherin and decreased expression of β-catenin and proteins in the Wnt signaling pathway. Moreover, LiCl (β-catenin activator) enhanced the regulatory effects of SOX17 on the expression of E-cadherin, promigratory cadherin, vimentin, and proteins in the Wnt signaling pathway, while XAV93920 (β-catenin inhibitor) exerted the opposite effect. The SOX17 N-terminus was proved to be necessary for these effects. Mechanistic investigations suggested SOX17 inhibits EC cell migration by inactivating the Wnt/β-catenin–epithelial mesenchymal transition (EMT) axis in EC cells.Conclusion: We uncovered a common SOX17–β-catenin–EMT mechanism underlying EC cell migration.Keywords: SOX17, endometrial cancer (EC), migration, high-mobility group (HMG)