Univ. Lille, Inserm, U1003 - PHYCEL - Physiologie Cellulaire, F-59000, Lille, France.
Laboratory of Excellence, Ion Channels Science and Therapeutics, Université de Lille, Villeneuve d'Ascq, France.
Cell Death Dis. 2019 Sep 9;10(9):652. doi: 10.1038/s41419-019-1891-8.
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.
在前列腺癌发生过程中，已知雄激素通过激活雄激素受体（AR）来控制瞬时受体电位 melastatin 8（TRPM8）蛋白的表达。TRPM8 通道的过度表达和/或活性被证明可抑制前列腺癌（PCa）细胞迁移。在这里，我们报告称，在某些浓度下，雄激素促进 PCa 细胞迁移。我们表明，潜在的机制是激活的 AR 通过与质膜脂质筏微域内的通道相互作用来抑制 TRPM8。因此，我们的研究确定了雄激素调节 TRPM8 通道的另一种非基因组机制，在开发新的治疗策略时应考虑这一机制。
