title: SOX17 is a tumor suppressor in endometrial cancer.
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.
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Yongli
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, International Peace Maternity & Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Bao
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Obstetrics and Gynecology, International Peace Maternity & Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Tong
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Wan
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D055760:SOXF Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C471298:MAML3 protein, human; D009687:Nuclear Proteins; C109188:SOX17 protein, human; D055760:SOXF Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D051176:beta Catenin
keywords: MAML3; SOX17; Wnt signaling; endometrial cancer; β-catenin