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 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.
Department of Obstetrics and Gynecology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, China.
Hui
H
Wang
Hua
H
Linghu
Jin
J
Wang
Ya-ling
YL
Che
Ting-xiu
TX
Xiang
Wei-xue
WX
Tang
Zhen-wei
ZW
Yao
D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000473:pathology*; D050737:Proto-Oncogene Proteins c-crk / Q000502:physiology*; D000089804:Shelterin Complex; D015398:Signal Transduction / Q000502:physiology*; D034501:Telomere-Binding Proteins / Q000502:physiology; D020744:rac GTP-Binding Proteins / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000502:physiology*
C485285:CRK protein, human; C099818:DOCK1 protein, human; D050737:Proto-Oncogene Proteins c-crk; C107953:RAC1 protein, human; D000089804:Shelterin Complex; C440809:TERF2IP protein, human; D034501:Telomere-Binding Proteins; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein