title: CrkI and p130(Cas)  complex regulates the migration and invasion of prostate cancer cells.
abstract: Prostate cancer metastasis is often associated with poor prognosis. The molecular coupling of the adaptor protein Crk to the docking protein p130(Cas) serves as a switch that regulates cell migration in several invasive cancer cells and Ack appears to act upstream of CrkII to modulate the cell motility. However, the precise role of Ack, Crk and p130(Cas) complex in prostate cancer migration remains unknown. In this study we examined the expression of Crk and p130(Cas) in prostate cancer cell lines, and found that CrkI and p130(Cas) protein level was higher in highly invasive PC-3M and PC-3 cell lines than in moderately invasive DU-145 cells. Upon shRNA mediated knockdown of CrkI and p130(Cas) in PC-3M cells, cell migration and invasion were significantly inhibited as analyzed by wound healing assay and transwell invasion assay. Furthermore, co-immunoprecipitation assay showed that p130(Cas) interacted with CrkI in PC-3M cells and the stability of p130(Cas) and CrkI depended on each other. AckI interacted with both CrkI and p130(Cas) and the interaction of AckI with CrkI seemed to be independent of p130(Cas) . Taken together, our results demonstrate the high expression of CrkI and p130(Cas) in invasive prostate cancer cells and the important role of CrkI/p130(Cas) complex in the migration and invasion of prostate cancer cells. These data suggest that CrkI/p130(Cas) could be exploited as potential molecular therapeutic target for prostate cancer metastasis.
authors.affiliation: Department of Urology, Xiangya Hospital, Central South University, Hunan, China.
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Dai
authors.forename: Lin
authors.initials: L
authors.lastname: Qi
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Minfeng
authors.initials: M
authors.lastname: Chen
authors.forename: Xiongbing
authors.initials: X
authors.lastname: Zu
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D050719:Crk-Associated Substrate Protein / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D050737:Proto-Oncogene Proteins c-crk / Q000235:genetics / Q000378:metabolism*
chemical_list: D050719:Crk-Associated Substrate Protein; D050737:Proto-Oncogene Proteins c-crk