title: Promotion of epithelial-mesenchymal transition by Frizzled2 is involved in the metastasis of endometrial cancer.
abstract: The Wnt signaling pathway is essential for embryonic development, and genetic alteration in this network is closely correlated with tumorigenesis and progression. Previous research has shown that Wnt receptor Frizzled2 (Fzd2) is elevated in many metastatic cancer cell lines and high grade tumors. Yet, little is known about the Fzd2 expression and activity in human endometrial cancer (EC). In this study, we present evidence of a direct role of Fzd2 in human EC. We found that Fzd2 expression was higher in EC than that in adjacent normal tissues, and was correlated with epithelial‑mesenchymal transition markers. Next, it was determined that the stable overexpression of Fzd2 in HEC-1B and Ishikawa cells promoted cell migration and induced an EMT phenotype. Conversely, RNA interference-mediated depletion of Fzd2 inhibited EC cell migration. Additionally, mechanistic investigation revealed that elevated Fzd2 expression activated canonical Wnt signaling and was blocked by canonical Wnt signaling inhibitor XAV939. However, Fzd2 did not influence the proliferation of EC cells. Thus, Fzd2 may be a potential marker for EC metastasis and a target for future therapies for this disease.
authors.affiliation: Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, P.R. China.
authors.forename: Yiding
authors.initials: Y
authors.lastname: Bian
authors.affiliation: Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, P.R. China.
authors.forename: Xinwen
authors.initials: X
authors.lastname: Chang
authors.affiliation: Department of Obstetrics and Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204, P.R. China.
authors.forename: Jingyun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200080, P.R. China.
authors.forename: Yiran
authors.initials: Y
authors.lastname: Li
authors.affiliation: Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204, P.R. China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Wan
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D051157:Frizzled Receptors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology*; D034622:RNA Interference / Q000502:physiology; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C489742:FZD2 protein, human; D051157:Frizzled Receptors