Wnt5b promotes the cell motility essential for metastasis of oral squamous cell carcinoma through active Cdc42 and RhoA
Wnt5b promotes the cell motility essential for metastasis of oral squamous cell carcinoma through active Cdc42 and RhoA
复制标题
DOI：
10.3892/ijo.2013.2172
复制
发表时间：
2014-01-01
影响因子：
5.2
通讯作者：
Yura, Yoshiaki
中科院分区：
文献类型：
--
作者：
Takeshita, Akinori;Iwai, Soichi;Yura, Yoshiaki
据报道，许多类型的鳞状细胞癌中都存在 Wnt 信号传导的激活。在这项研究中，我们利用具有不同转移潜能的人口腔鳞状细胞癌（OSCC）细胞，研究了Wnt信号传导在转移中的作用。此外，我们的目的是阐明与高转移潜能相关的特征生物学特征，并确定抑制 OSCC 淋巴结转移的新靶分子。我们比较了 SAS-Venus（表达绿色荧光蛋白的 SAS OSCC 细胞）和 SAS-LM8，SAS-LM8 是通过体内选择从 SAS-Venus 衍生的高度转移细胞系。与SAS-Venus相比，SAS-LM8细胞系具有更强的迁移和侵袭能力。此外，与SAS-Venus细胞相比，SAS-LM8细胞中产生更多数量的丝状伪足样突起结构，并且与SAS-Venus细胞相比，SAS-LM8细胞中活性Cdc42和活性RhoA蛋白的水平更高。我们没有观察到两种细胞系之间 Wnt/-catenin 靶基因的表达存在任何差异；然而，与 SAS-Venus 细胞相比，SAS-LM8 细胞中 Wnt5b 的 mRNA 水平较高。为了证实 Wnt5b 参与 OSCC 细胞的迁移，我们检查了 SAS-Venus 细胞和 SAS-LM8 细胞中 siRNA 介导的 Wnt5b 敲低的效果。 siRNA处理显着抑制迁移和丝状伪足样突出结构的形成。相反，当用Wnt5b刺激时，丝状伪足样突起的迁移和形成显着增强，活性Cdc42和活性RhoA蛋白的水平也增加。这些结果表明Wnt5b通过活性Cdc42和RhoA参与OSCC细胞的迁移能力。
The activation of Wnt signaling has been reported in many types of squamous cell carcinoma. In this study, using human oral squamous cell carcinoma (OSCC) cells with different metastatic potential, we investigated the involvement of Wnt signaling in metastasis. Further, we aimed to elucidate the characteristic biological features related to high metastatic potential and to identify new target molecules for the suppression of OSCC lymph node metastasis. We compared SAS-Venus (SAS OSCC cells expressing green fluorescent protein) and SAS-LM8, which is a highly metastatic cell line derived from SAS-Venus by in vivo selection. The SAS-LM8 cell line had greater ability of migration and invasion compared to SAS-Venus. Furthermore, a higher number of filopodia-like protrusive structures were produced in SAS-LM8 cells compared to SAS-Venus cells, and the levels of active Cdc42 and active RhoA protein were higher in SAS-LM8 cells compared to SAS-Venus cells. We did not observe any differences in the expression of Wnt/-catenin target genes between the two cell lines; however, the mRNA levels of Wnt5b were higher in SAS-LM8 cells compared to SAS-Venus cells. To confirm the involvement of Wnt5b in migration in OSCC cells, we examined the effects of the siRNA-mediated knockdown of Wnt5b in SAS-Venus cells and SAS-LM8 cells. The siRNA treatment significantly inhibited migration and the formation of filopodia-like protrusive structures. Conversely, when stimulated with Wnt5b, the migration and formation of filopodia-like protrusions were significantly enhanced and the levels of active Cdc42 and active RhoA proteins were also increased. These results indicate that Wnt5b is involved in the migration ability of OSCC cells through active Cdc42 and RhoA.