The role of Crk/Dock180/Rac1 pathway in the malignant behavior of human ovarian cancer cell SKOV3
The role of Crk/Dock180/Rac1 pathway in the malignant behavior of human ovarian cancer cell SKOV3
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DOI：
10.1007/s13277-009-0009-9
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发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Yao, Zhen-wei
中科院分区：
文献类型：
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作者：
Wang, Hui;Linghu, Hua;Yao, Zhen-wei
小的GTP酶，特别是Rho家族，是细胞运动和迁移的关键调节因子。Dock180是已知的信号适配蛋白Crk的主要靶标，是小GTP酶rac1的鸟嘌呤核苷酸交换因子。在目前的研究中，发现Dock180主要与CrkI结合，而不是CrkII，它与ELMO1的相关性也在卵巢癌细胞SKOV3中得到证实。为了评价Dock180在人卵巢癌细胞中的作用，我们使用小干扰RNA表达载体在SKOV3细胞中进行了RNAi介导的Dock180的敲除。在Dock180基因敲除细胞中，我们发现ELMO1的表达和rac1的活性同时降低。相比之下，另一种Crk结合分子C3G的表达和Rap1活性均明显增加。因此，所有Dock180基因敲除的细胞都出现了明显的细胞形态变化，细胞增殖减少，细胞迁移减弱。综上所述，这些结果表明，Crk/Dock180/rac1的信号转导参与了肌动蛋白细胞骨架的重组，从而参与了人卵巢癌细胞株SKOV3的细胞增殖、运动、侵袭和侵袭。
Small GTPases, particularly the Rho family, are key regulators of cell motility and migration. Dock180 was well known for the main target of signal adaptor protein Crk and acted as a guanine-nucleotide exchange factor for small GTPase Rac1. In the present study, Dock180 was found to combine primarily with CrkI other than CrkII, and its association with Elmo1 was also demonstrated in ovarian cancer cell SKOV3. To evaluate the role of Dock180 in human ovarian cancer cell, we performed RNAi-mediated knockdown of Dock180 in SKOV3 cells using small interfering RNA expression vector. In Dock180 knockdown cells, we found that Elmo1 expression and Rac1 activity were decreased simultaneously. By contrast, the expressions of both another Crk-combining molecule C3G and Rap1 activity were observed to increase obviously. Accordingly, all Dock180 knockdown cells present with evident change in cell morphology, reduced cell proliferation, and attenuated cell migration. Taken together, these results suggest that signal transfer of Crk/Dock180/Rac1 is implicated in actin cytoskeleton reorganization and thus in the cell proliferation, motility, invasion, and of human ovarian cancer cell line SKOV3.