ErbB-2 via PYK2 upregulates the adhesive ability of androgen receptor-positive human prostate cancer cells

• Published in: Oncogene Vol. 26; no. 54; pp. 7552 - 7559
• Main Authors: YUAN, T. C, LIN, F. F, VEERAMANI, S, CHEN, S. J, EARP, H. S, LIN, M. F
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 29.11.2007; Nature Publishing Group
• Subjects: Adhesives; Androgen receptors; Androgens; Biological and medical sciences; Cancer cells; Cell activation; Cell adhesion; Cell adhesion & migration; Cell Adhesion - physiology; Cell Line, Tumor; Cell physiology; Cell receptors; Cell structures and functions; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Enzyme Inhibitors - pharmacology; ErbB protein; ErbB-2 protein; Focal Adhesion Kinase 2 - metabolism; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation, Neoplastic; Genes; Genetic aspects; Gynecology. Andrology. Obstetrics; Hormone receptors; Humans; Male; Male genital diseases; MAP kinase; Medical sciences; MEK inhibitors; Metastases; Miscellaneous; Molecular and cellular biology; Organic Chemicals - pharmacology; Physiological aspects; Prostate cancer; Prostatic Neoplasms; Protein kinases; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; Receptors, Androgen - physiology; Recombinant Proteins - metabolism; Transfection; Tumors; United States; Human; ErbB-2; Urinary system disease; Prostate disease; Androgen; Malignant tumor; Carcinogenesis; PYK2; Cell adhesion; Sex steroid hormone; Male genital diseases; Prostate cancer; Cancer; Biological receptor
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1210570

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.