Abstract
Aberrant regulation in the adhesive ability of cancer cells is closely associated with their metastatic activity. In this study, we examine the role of ErbB-2 in regulating the adhesive ability of androgen receptor (AR)-positive human prostate cancer (PCa) cells, the major cell population of PCa. Utilizing different LNCaP and MDA PCa2b cells as model systems, we found that ErbB-2 activity was correlated with PYK2 activity and adhesive ability in those cells. Increased ErbB-2 expression or activity in LNCaP C-33 cells enhanced PYK2 activation and cell adhesion, while the high PYK2 activity and the rapid adhesion of LNCaP C-81 cells were decreased by diminishing ErbB-2 expression or activity. Knockdown studies revealed the predominant role of ErbB-2 in regulating LNCaP C-81 cell adhesion. Coimmunoprecipitation showed that C-81 cells had increased interaction between ErbB-2 and PYK2. Elevated ErbB-2 activity in LNCaP cells correlated with increased ERK/MAPK activity and enhanced adhesive ability, which were abolished by the expression of K457A-PYK2 mutant or the treatment of PD98059, a MEK inhibitor. In summary, our data suggested that ErbB-2, via PYK2-ERK/MAPK, upregulates the adhesive ability of AR-positive human PCa cells.
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Acknowledgements
We thank Dr Chawnshang Chang at University of Rochester (Rochester, NY, USA) for the gift of the wt and the K457A mutant of PYK2 cDNAs. We also thank Dr Yaping Tu at Creighton University (Omaha, NE, USA) for providing us with CWR22Rv1 cells, and Dr Ming-Shyue Lee for analysing FAK activation in LNCaP cells. This study was supported in part by NIH grant CA88184, DOD Army PCa program PC050769, Nebraska Research Initiative and UNMC Graduate Student Fellowship
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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).
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Yuan, TC., Lin, FF., Veeramani, S. et al. ErbB-2 via PYK2 upregulates the adhesive ability of androgen receptor-positive human prostate cancer cells. Oncogene 26, 7552–7559 (2007). https://doi.org/10.1038/sj.onc.1210570
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DOI: https://doi.org/10.1038/sj.onc.1210570