ERK5 signalling in prostate cancer promotes an invasive phenotype

Ramsay, A.K. et al. (2011) ERK5 signalling in prostate cancer promotes an invasive phenotype. British Journal of Cancer, 104(4), pp. 664-672. (doi:10.1038/sj.bjc.6606062)

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Publisher's URL: http://dx.doi.org/10.1038/sj.bjc.6606062

Abstract

<p><b>Background:</b> Aberrant mitogen/extracellular signal-regulated kinase 5 (MEK5)-extracellular signal-regulated protein kinase 5 (ERK5)-mediated signalling has been implicated in a number of tumour types including prostate cancer (PCa). The molecular basis of ERK5-driven carcinogenesis and its clinical relevance remain to be fully characterised.</p> <p><b>Methods:</b> Modulation of ERK5 expression or function in human PCa PC3 and PC3-ERK5 (stably transfected with ERK5) cells was performed using siRNA-mediated knockdown or the MEK inhibitor PD18435 respectively. <i>In vitro</i> significance of ERK5 signalling was assessed by assays for proliferation, motility, invasion and invadopodia. Expression of matrix metalloproteinases/tissue inhibitors of metalloproteases was determined by Q-RT-PCR. Extracellular signal-regulated protein kinase 5 expression in primary and metastatic PCa was examined using immunohistochemistry.</p> <p><b>Results:</b> Reduction of ERK5 expression or signalling significantly inhibited the motility and invasive capability of PC3 cells. Extracellular signal-regulated protein kinase 5-mediated signalling significantly promoted formation of <i>in vivo</i> metastasis in an orthotopic PCa model (P < 0.05). Invadopodia formation was also enhanced by forced ERK5 expression in PC3 cells. Furthermore, in metastatic PCa, nuclear ERK5 immunoreactivity was significantly upregulated when compared with benign prostatic hyperplasia and primary PCa (P = 0.013 and P < 0.0001, respectively).</p> <p><b>Conclusion:</b> Our <i>in vitro</i>, <i>in vivo</i> and clinical data support an important role for the MEK5-ERK5 signalling pathway in invasive PCa, which represents a potential target for therapy in primary and metastatic PCa.</p>

Item Type:Articles
Keywords:Prostate cancer, signalling, invasive phenotype
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ahmad, Dr Imran and Leung, Professor Hing and Marquez, Dr Rudi and Machesky, Professor Laura
Authors: Ramsay, A.K., McCracken, S.R.C., Soofi, M., Fleming, J., Yu, A.X., Ahmad, I., Morland, R., Machesky, L., Nixon, C., Edwards, D.R., Nuttall, R.K., Seywright, M., Marquez, R., Keller, E., and Leung, H.Y.
Subjects:R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Science and Engineering > School of Chemistry
Journal Name:British Journal of Cancer
Publisher:Nature Publishing Group
ISSN:0007-0920
ISSN (Online):1532-1827
Published Online:25 January 2011

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