Oncotarget

Research Papers:

SOX17 is a tumor suppressor in endometrial cancer

Yongli Zhang, Wei Bao, Kai Wang, Wen Lu, Huihui Wang, Huan Tong and Xiaoping Wan _

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Oncotarget. 2016; 7:76036-76046. https://doi.org/10.18632/oncotarget.12582

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Abstract

Yongli Zhang1, Wei Bao2, Kai Wang1, Wen Lu1, Huihui Wang2, Huan Tong3, Xiaoping Wan1

1Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China

2Department of Obstetrics and Gynecology, International Peace Maternity & Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

3Department of Obstetrics and Gynecology, Shanghai First People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China

Correspondence to:

Xiaoping Wan, email: wanxiaoping@tongji.edu.cn

Keywords: SOX17, MAML3, endometrial cancer, β-catenin, Wnt signaling

Received: January 10, 2016    Accepted: September 26, 2016    Published: October 12, 2016

ABSTRACT

β-catenin is a key regulatory factor for the Wnt signaling pathway. SOX17 is an important β-catenin inhibitor, while MAML3 is a co-activator of β-catenin-mediated transcription. Out of 120 endometrial cancer (EC) patients, we found that those with tumors expressing higher SOX17 (n=68) had longer recurrence-free survival (P=0.024), while higher MAML3 expression (n=76) was associated with shorter recurrence-free survival (P=0.022). Immunohistochemical and immunoprecipitation analyses revealed that SOX17 and MAML3 co-localized in EC cell nuclei, and the MAML3 C-terminal region was necessary for SOX17 binding. SOX17 regulated MAML3 transcription via binding to the MAML3 promoter, decreasing Wnt pathway protein expression and suppressing EC cell growth and colony formation in vitro. In nude mice, SOX17 over-expression inhibited tumor growth, and co-inhibition or co-overexpression of SOX17 and MAML3 rescued this response. Our results suggest that decreasing SOX17 levels may promote EC development and progression, and that by downregulating MAML3 expression and Wnt signaling, SOX17 acts as a tumor suppressor that may improve outcome in patients with EC.


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