The role of Crk/Dock180/Rac1 pathway in the malignant behavior of human ovarian cancer cell SKOV3

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 primaril...

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Bibliographic Details
Published in:Tumor biology 2010-01, Vol.31 (1), p.59-67
Main Authors: Wang, Hui, Linghu, Hua, Wang, Jin, Che, Ya-ling, Xiang, Ting-xiu, Tang, Wei-xue, Yao, Zhen-wei
Format: Article
Language:English
Subjects:
Biomedical and Life Sciences
Biomedicine
Cancer Research
Cell Line, Tumor
Cell Movement
Cell Proliferation
Cellular biology
Female
Humans
Motility
Ovarian cancer
Ovarian Neoplasms - pathology
Proteins
Proto-Oncogene Proteins c-crk - physiology
rac GTP-Binding Proteins - physiology
rac1 GTP-Binding Protein - physiology
Research Article
Signal Transduction - physiology
Telomere-Binding Proteins - physiology
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Summary: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.
ISSN:1010-4283
1423-0380
DOI:10.1007/s13277-009-0009-9