The role of Crk/Dock180/Rac1 pathway in the malignant behavior of human ovarian cancer cell SKOV3
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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.
KeywordsCrk DOCK180 Rac1 C3G Human ovarian cancer
We thank Dr. Qiou Wei in Center for Cancer Research, National Cancer Institute at Frederick, MD, USA, for his technical support. This work was supported by the grant from the National Natural Science Foundation of China (NSFC no. C30672432, no.C30772330) and was supported partly by the Natural Science Foundation Project of CQ CSTC, 2007BB5319, the grant for returned students abroad from the Ministry of Education of the People's Republic of China(2007), and the grant for Medical Sciences from the First Hospital, Chongqing Medical University (YXJJ2009-06).
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