Regulation of cell-cell contact molecules and the metastatic phenotype of medullary thyroid carcinoma by the Raf-1/MEK/ERK pathway.
Regulation of cell-cell contact molecules and the metastatic phenotype of medullary thyroid carcinoma by the Raf-1/MEK/ERK pathway.
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DOI：
10.1016/j.surg.2008.07.020
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发表时间：
2008-12
期刊：
影响因子：
3.8
通讯作者：
Chen, Herbert
中科院分区：
文献类型：
--
作者：
Ning, Li;Kunnimalaiyaan, Muthusamy;Chen, Herbert
甲状腺髓样癌（MTC）是高度转移的。我们最近报道了MTC细胞中Raf-1/MEK/ERK信号通路的激活导致形态学改变。我们假设Raf-1诱导的形态学改变可能与细胞-细胞接触分子的改变有关，从而影响MTC细胞的转移潜力。本研究采用雌二醇（E2）诱导的Raf-1 MTC细胞系（TT-raf）。Western blot分析证实了Raf-1/MEK/ERK通路的激活，并测量了细胞-细胞接触分子的水平。通过细胞粘附和迁移实验研究细胞的运动特性。E2处理TT-raf细胞导致Raf-1/MEK/ERK通路激活，磷酸化mek1 /2和-ERK1/2水平升高。这导致必要的细胞-细胞接触分子水平显著降低，包括e -钙粘蛋白、β-连环蛋白和occludin。重要的是，Raf-1/ MEK/ERK通路的激活和相关的基本细胞-细胞接触分子的减少显著抑制了MTC细胞的粘附和迁移能力。此外，用MEK特异性抑制剂U0126处理raf -1激活的细胞，消除了这些raf -1诱导的效应，这表明对MTC细胞转移表型的抑制是MEK依赖的途径。这些数据表明，Raf-1/MEK/ERK通路调节MTC细胞的基本细胞-细胞接触分子和转移表型。因此，这些发现为MTC转移进展的关键步骤提供了进一步的见解。
Medullary thyroid carcinoma (MTC) is highly metastatic. We have recently reported that activation of the Raf-1/MEK/ERK signaling pathway in MTC cells results in morphologic changes. We hypothesized that Raf-1--induced morphologic changes could be associated with alterations in cell--cell contact molecules, thereby affecting the metastatic potential of MTC cells. An estradiol (E2)-inducible Raf-1 MTC cell line (TT-raf) was utilized in this study. Western blot analysis was used to confirm the Raf-1/MEK/ERK pathway activation and to measure levels of essential cell–cell contact molecules. Assays for cell adhesion and migration were performed to investigate the cell motility. E2 treatment of TT-raf cells resulted in the Raf-1/MEK/ERK pathway activation as evidenced by increased levels of phospho-MEK1/2 and -ERK1/2. This resulted in significant reductions in levels of essential cell–cell contact molecules including E-cadherin, β-catenin, and occludin. Importantly, activation of the Raf-1/ MEK/ERK pathway and the associated decrease in essential cell–cell contact molecules dramatically inhibited the abilities of adhesion and migration in MTC cells. Furthermore, treatment of Raf-1–activated cells with U0126, a specific inhibitor of MEK, abrogated these Raf-1–induced effects indicating that the suppression of the metastatic phenotype in MTC cells is a MEK-dependent pathway. These data suggest that the Raf-1/MEK/ERK pathway regulates essential cell--cell contact molecules and metastatic phenotype of MTC cells. Thus, these findings provide further insight into the key steps in the metastatic progression of MTC.
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影响因子：
2.3
作者：
Vaccaro, Abram;Chen, Herbert;Kunnimalaiyaan, Muthusamy
通讯作者：
Kunnimalaiyaan, Muthusamy
影响因子：
2.9
作者：
Wu, Colleen;Cipollone, Jane;Roskelley, Calvin D.
通讯作者：
Roskelley, Calvin D.
影响因子：
2.8
作者：
Park, Daehoon;Karesen, Rolf;Sauer, Torill
通讯作者：
Sauer, Torill
DOI：
10.2741/2075
发表时间：
2007-01-01
期刊：
FRONTIERS IN BIOSCIENCE
影响因子：
--
作者：
Hlubek, Falk;Spaderna, Simone;Brabletz, Thomas
通讯作者：
Brabletz, Thomas
影响因子：
9
作者：
Chen, HB;Roberts, JR;Bulkley, GB
通讯作者：
Bulkley, GB