Cao Ting-Ting, Xiang Di, Liu Bei-Lei, Huang Tu-Xiong, Tan Bin-Bin, Zeng Chui-Mian, Wang Zhong-Yuan, Ming Xiao-Yan, Zhang Li-Yi, Jin Guangyi, Li Feng, Wu Jian-Lin, Guan Xin-Yuan, Lu Desheng, Fu Li
Department of Pharmacology and Cancer Research Centre, School of Medicine, Shenzhen University, Shenzhen, China.
Department of Clinical Oncology, The University of Hong Kong Faculty of Medicine, Hong Kong, China.
Oncotarget. 2017 Jul 26;8(39):65957-65968. doi: 10.18632/oncotarget.19586. eCollection 2017 Sep 12.
Frizzled (FZD) proteins are receptors for secreted WNT proteins and play a critical role in the malignant progression of various cancers. However, the role of human FZD family members in esophageal squamous cell carcinoma (ESCC) was rarely investigated. In this study, we found that the gene was the most commonly up-regulated member in ESCC cell lines compared with other . TMA studies further validated that FZD7 protein was up-regulated in 165 of 252 (65.5%) informative ESCC patients and significantly correlated with poor overall survival (P=0.001). Additionally, multivariate Cox regression analysis showed that FZD7 overexpression was an independent prognostic factor for ESCC patients. Ectopic expression of could promote ESCC cell metastasis both and . Under WNT3A stimulation, FZD7 was able to induce the nuclear translocation of β-catenin and activate the downstream targets of WNT/β-catenin signaling, as well as promote epithelial-mesenchymal transition (EMT) potential in ESCC cells. Our study demonstrated for the first time that FZD7 contributes to the malignant progression of ESCC and represents a novel prognostic marker and a potential therapeutic target for ESCC patients.
卷曲蛋白（FZD）是分泌型WNT蛋白的受体，在多种癌症的恶性进展中起关键作用。然而，人类FZD家族成员在食管鳞状细胞癌（ESCC）中的作用鲜有研究。在本研究中，我们发现与其他[未提及的相关事物]相比，[未明确指出的基因]是ESCC细胞系中最常上调的成员。组织微阵列（TMA）研究进一步证实，在252例有信息的ESCC患者中，165例（65.5%）的FZD7蛋白上调，且与总体生存率差显著相关（P = 0.001）。此外，多因素Cox回归分析表明，FZD7过表达是ESCC患者的独立预后因素。[未明确指出的事物]的异位表达可促进ESCC细胞在[未明确指出的两种情况]下发生转移。在WNT3A刺激下，FZD7能够诱导β-连环蛋白的核转位，激活WNT/β-连环蛋白信号的下游靶点，并促进ESCC细胞的上皮-间质转化（EMT）潜能。我们的研究首次证明FZD7促进ESCC的恶性进展，是ESCC患者一种新的预后标志物和潜在治疗靶点。
