FZD7 is a novel prognostic marker and promotes tumor metastasis via WNT and EMT signaling pathways in esophageal squamous cell carcinoma.
FZD7 is a novel prognostic marker and promotes tumor metastasis via WNT and EMT signaling pathways in esophageal squamous cell carcinoma.
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FZD7 是一种新型预后标志物，通过 WNT 和 EMT 信号通路促进食管鳞状细胞癌的肿瘤转移。
DOI：
10.18632/oncotarget.19586
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发表时间：
2017-09-12
期刊：
影响因子：
--
通讯作者：
Fu L
中科院分区：
文献类型：
--
作者：
Cao TT;Xiang D;Liu BL;Huang TX;Tan BB;Zeng CM;Wang ZY;Ming XY;Zhang LY;Jin G;Li F;Wu JL;Guan XY;Lu D;Fu L
卷曲蛋白（FZD）是分泌WNT蛋白的受体，在各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）中的作用很少被研究。本研究发现，与其他FZD相比，FZD7基因是ESCC细胞系中最常见的上调FZD成员。TMA研究进一步证实，252例ESCC患者中165例（65.5%）FZD7蛋白表达上调，且与较差的总生存率显著相关（P=0.001）。此外，多因素Cox回归分析显示，FZD7过表达是ESCC患者的独立预后因素。FZD7异位表达在体外和体内均能促进ESCC细胞转移。在WNT3A刺激下，FZD7能够诱导β-catenin的核易位，激活WNT/β-catenin信号传导的下游靶点，促进ESCC细胞上皮-间质转化（epithelial-mesenchymal transition， EMT）电位。我们的研究首次证明FZD7与ESCC的恶性进展有关，并代表了ESCC患者的一种新的预后标志物和潜在的治疗靶点。
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 FZD7 gene was the most commonly up-regulated FZD member in ESCC cell lines compared with other FZDs. 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 FZD7 could promote ESCC cell metastasis both in vitro and in vivo. 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.
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影响因子：
3.7
作者：
Song J;Gao L;Yang G;Tang S;Xie H;Wang Y;Wang J;Zhang Y;Jin J;Gou Y;Yang Z;Chen Z;Wu K;Liu J;Fan D
通讯作者：
Fan D
影响因子：
254.7
作者：
Torre, Lindsey A.;Bray, Freddie;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
11.2
作者：
Gupta, Santosh;Iljin, Kristiina;Kallioniemi, Olli
通讯作者：
Kallioniemi, Olli
DOI：
10.1038/nrm3758
发表时间：
2014-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.4
作者：
Deng, Boya;Zhang, Siyang;Guo, Kejun
通讯作者：
Guo, Kejun