CrkI and p130Cas complex regulates the migration and invasion of prostate cancer cells

Prostate cancer metastasis is often associated with poor prognosis. The molecular coupling of the adaptor protein Crk to the docking protein p130Cas 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 p130Cas complex in prostate cancer migration remains unknown. In this study we examined the expression of Crk and p130Cas in prostate cancer cell lines, and found that CrkI and p130Cas 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 p130Cas 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 p130Cas interacted with CrkI in PC‐3M cells and the stability of p130Cas and CrkI depended on each other. AckI interacted with both CrkI and p130Cas and the interaction of AckI with CrkI seemed to be independent of p130Cas. Taken together, our results demonstrate the high expression of CrkI and p130Cas in invasive prostate cancer cells and the important role of CrkI/p130Cas complex in the migration and invasion of prostate cancer cells. These data suggest that CrkI/p130Cas could be exploited as potential molecular therapeutic target for prostate cancer metastasis. Copyright © 2011 John Wiley & Sons, Ltd.

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