AEG-1 activates Wnt/PCP signaling to promote metastasis in tongue squamous cell carcinoma.
AEG-1 activates Wnt/PCP signaling to promote metastasis in tongue squamous cell carcinoma.
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AEG-1激活Wnt/PCP信号促进舌鳞状细胞癌转移
DOI：
10.18632/oncotarget.6573
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发表时间：
2016-01-12
期刊：
影响因子：
--
通讯作者：
Ke Z
中科院分区：
文献类型：
--
作者：
Pan Y;Guo X;Yang Z;Chen S;Lei Y;Lin M;Wang L;Feng C;Ke Z
尽管在治疗方面取得了进展，但局部晚期舌鳞状细胞癌（TSCC）和颈部淋巴结转移患者的生存率仍然很低。在此，我们评估AEG-1对TSCC转移的功能作用，并探讨AEG-1刺激上皮-间质转化（EMT）的分子机制。我们最初发现AEG-1 mRNA水平在转移性TSCC中比在非转移性TSCC中高得多，并且AEG-1表达与EMT状态密切相关。受试者工作特征分析显示AEG-1和EMT状态联合可预测TSCC患者的生存率。此外，AEG-1敲低抑制培养的TSCC细胞系和异种移植物-小鼠模型中的EMT。重组AEG-1激活Wnt/PCP-Rho信号，其对TSCC细胞侵袭力和EMT的刺激作用可被抗Wnt 5a中和抗体或Rac 1或ROCK抑制剂逆转。这些结果强调了AEG-1对癌细胞侵袭力和EMT的关键刺激作用，并表明AEG-1可能是TSCC患者有用的预后生物标志物。
Despite advances in therapy, survival among patients with locally advanced squamous cell carcinoma of tongue (TSCC) and cervical lymph node metastasis remains dismal. Here, we estimated the functional effect of AEG-1 on TSCC metastasis and explored the molecular mechanism by which AEG-1 stimulates epithelial-mesenchymal transition (EMT). We initially found that AEG-1 mRNA levels were much higher in metastatic TSCC than in non-metastatic TSCC and that AEG-1 expression strongly correlates with EMT status. Receiver operating characteristic analysis showed that the combined AEG-1 and EMT statuses are predictive of the survival rate among TSCC patients. In addition, AEG-1 knockdown inhibited EMT in cultured TSCC cell lines and in a xenograft-mouse model. Recombinant AEG-1 activated Wnt/PCP-Rho signaling, and its stimulatory effects on TSCC cell invasiveness and EMT were reversed by an anti-Wnt5a neutralizing antibody or by inhibition of Rac1 or ROCK. These results highlight the critical stimulatory effect of AEG-1 on cancer cell invasiveness and EMT and indicate that AEG-1 may be a useful prognostic biomarker for TSCC patients.