Tiam1 promotes thyroid carcinoma metastasis by modulating EMT via Wnt/β-catenin signaling
Tiam1 promotes thyroid carcinoma metastasis by modulating EMT via Wnt/β-catenin signaling
复制标题
Tiam1 通过 Wnt/β-catenin 信号传导调节 EMT 促进甲状腺癌转移
DOI：
10.1016/j.yexcr.2017.12.019
复制
发表时间：
2018-01-15
影响因子：
3.7
通讯作者：
Zhang, Xiaoping
中科院分区：
文献类型：
--
作者：
Liu, Lin;Wu, Bo;Zhang, Xiaoping
鸟嘌呤核苷酸交换因子Tiam 1的异常表达与许多癌症的侵袭性表型有关。然而，其在甲状腺癌和下游分子事件的参与仍然在很大程度上不确定。在此，我们研究了Tiam 1在体外和体内对甲状腺癌侵袭和转移的影响，并通过研究Tiam 1表达的调节和受影响的下游通路来探讨其潜在机制。我们的研究结果表明，Tiam 1敲低抑制甲状腺癌细胞的迁移和侵袭能力，抑制上皮间质转化（EMT），并抑制Wnt/β-连环蛋白信号在体外。此外，Tiam 1敲低抑制体内肝转移的发展。Tiam 1对Wnt/β-catenin途径介导的转移和EMT的作用被Rac 1沉默逆转，表明Tiam 1的促转移作用是由Rac 1的激活介导的。这些结果表明Tiam 1可能是甲状腺癌治疗的预后因子和潜在的治疗靶点。
Aberrant expression of the guanine nucleotide exchange factor Tiam1 is implicated in the invasive phenotype of many cancers. However, its involvement in thyroid carcinoma and downstream molecular events remains largely undefined. Here, we examined the effects of Tiam1 on the invasiveness and metastasis of thyroid carcinoma in vitro and in vivo and explored the underlying mechanisms by investigating the regulation of Tiam1 expression and the downstream pathways affected. Our results showed that Tiam1 knockdown inhibited the migratory and invasive capacity of thyroid cancer cells, suppressed epithelial-mesenchymal transition (EMT), and inhibited Wnt/beta-catenin signaling in vitro. Moreover, Tiam1 knockdown suppressed liver metastasis development in vivo. The effects of Tiam1 on metastasis and EMT mediated by the Wnt/beta-catenin pathway were reversed by Rac1 silencing, suggesting that the prometastatic effect of Tiam1 is mediated by the activation of Rac1. These results indicate that Tiam1 may be a prognostic factor and potential therapeutic target for the treatment of thyroid cancers.