Bian Yiding, Chang Xinwen, Liao Yun, Wang Jingyun, Li Yiran, Wang Kai, Wan Xiaoping
Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, P.R. China.
Department of Obstetrics and Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, P.R. China.
Oncol Rep. 2016 Aug;36(2):803-10. doi: 10.3892/or.2016.4885. Epub 2016 Jun 17.
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.
Wnt信号通路对胚胎发育至关重要，该网络中的基因改变与肿瘤发生和进展密切相关。先前的研究表明，Wnt受体卷曲蛋白2（Fzd2）在许多转移性癌细胞系和高级别肿瘤中表达升高。然而，关于Fzd2在人类子宫内膜癌（EC）中的表达和活性知之甚少。在本研究中，我们提供了Fzd2在人类EC中直接作用的证据。我们发现，Fzd2在EC中的表达高于相邻正常组织，且与上皮-间质转化标志物相关。接下来，确定Fzd2在HEC-1B和Ishikawa细胞中的稳定过表达促进细胞迁移并诱导EMT表型。相反，RNA干扰介导的Fzd2缺失抑制了EC细胞迁移。此外，机制研究表明，Fzd2表达升高激活了经典Wnt信号通路，并被经典Wnt信号抑制剂XAV939阻断。然而，Fzd2不影响EC细胞的增殖。因此，Fzd2可能是EC转移的潜在标志物，也是该疾病未来治疗的靶点。
