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PSA reduces prostate cancer cell motility by stimulating TRPM8 activity and plasma membrane expression

Oncogene volume 29, pages 4611–4616 (2010)Cite this article

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Abstract

Although the transient receptor potential melastatin 8 (TRPM8) cold receptor is highly expressed in prostate cancer (PCa) and constitutes a promising diagnostic and prognostic indicator, the natural agonists of this channel in the prostate, as well as its physiological and pathological functions, remain unknown. In this study, we identified the well-known PCa marker, prostate-specific antigen (PSA), as a physiological TRPM8 agonist. Electrophysiological and Ca2+ imaging studies demonstrated that PSA activated TRPM8-mediated current by the bradykinin 2 receptor signaling pathway. Further investigation of this mechanism by cell-surface biotinylation revealed that the increase in TRPM8 current induced by PSA was due to an increase in the number of functional TRPM8 channels on the plasma membrane. Importantly, wound-healing and migration assays revealed that TRPM8 activation by PSA reduced motility of the PC3 PCa cell line, suggesting that plasma membrane TRPM8 has a protective role in PCa progression. Consequently, PSA was identified as a natural TRPM8 agonist in the prostate and we propose a putative physiological role for both of these proteins in carcinogenesis, making this pathway a potentially important target for anticancer agent development.

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Acknowledgements

This study was supported by grants from the Institut national de la Santé et de la Recherche Médicale (INSERM), Ministère de l’éducation nationale and the Ligue Nationale contre le cancer. Dr D Gkika was supported by a grant from the Institut National du Cancer (INCa) (Grant N°: 07/3d1616/pdoc-110-18/ng-nc).

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Author notes

  1. M Flourakis

    Present address: 3Current address: Center for Sleep and Circadian Biology, Department of Neurobiology and Physiology, Northwestern University, 2205 Tech Drive, #2-160, Evanston, IL 60208, USA.,

  2. D Gkika and M Flourakis: These authors contributed equally to this work.

Authors and Affiliations

  1. Inserm, U1003, Equipe labellisée par la Ligue Nationale contre le cancer, Villeneuve d’Ascq, France

    D Gkika, M Flourakis, L Lemonnier & N Prevarskaya

  2. Université des Sciences et Technologies de Lille, Villeneuve d’Ascq, France

    D Gkika, M Flourakis, L Lemonnier & N Prevarskaya

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  1. D Gkika
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  2. M Flourakis
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  3. L Lemonnier
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  4. N Prevarskaya
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Correspondence to N Prevarskaya.

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Gkika, D., Flourakis, M., Lemonnier, L. et al. PSA reduces prostate cancer cell motility by stimulating TRPM8 activity and plasma membrane expression. Oncogene 29, 4611–4616 (2010). https://doi.org/10.1038/onc.2010.210

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