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

Guillaume P. Grolez (1) , Dmitri V. Gordiendko (1) , Manon Clarisse (1) , Mehdi Hammadi (2) , Emilie Desruelles (1) , Gaëlle Fromont (3) , Natalia Prevarskaya (1) , Christian Slomianny (1) , Dimitra Gkika (1)

1 PHYCELL - Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003
2 IEMN - Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520
3 N2Cox - Niche, Nutrition, Cancer et métabolisme oxydatif

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.

Domaines: Cancer; Urologie et Néphrologie; Organisation et fonctions cellulaires [q-bio.SC]

Guillaume P. Grolez, Dmitri V. Gordiendko, Manon Clarisse, Mehdi Hammadi, Emilie Desruelles, et al.. TRPM8-androgen receptor association within lipid rafts promotes prostate cancer cell migration. Cell Death and Disease, 2019, 10 (9), pp.652. ⟨10.1038/s41419-019-1891-8⟩. ⟨hal-03133861⟩