TRPM8-androgen receptor association within lipid rafts promotes prostate cancer cell migration

脂筏内的 TRPM8-雄激素受体结合促进前列腺癌细胞迁移

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作者:Guillaume P Grolez, Dmitri V Gordiendko, Manon Clarisse, Mehdi Hammadi, Emilie Desruelles, Gaëlle Fromont, Natalia Prevarskaya, Christian Slomianny, Dimitra Gkika

Abstract

In prostate carcinogenesis, androgens are known to control the expression of the transient receptor potential melastatin 8 (TRPM8) protein via activation of androgen receptor (AR). Overexpression and/or activity of TRPM8 channel was shown to suppress prostate cancer (PCa) cell migration. Here we report that at certain concentrations androgens facilitate PCa cell migration. We show that underlying mechanism is inhibition of TRPM8 by activated AR which interacts with the channel within lipid rafts microdomains of the plasma membrane. Thus, our study has identified an additional nongenomic mechanism of the TRPM8 channel regulation by androgens that should be taken into account upon the development of novel therapeutic strategies.

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