Prostate cell differentiation status determines transient receptor potential melastatin member 8 channel subcellular localization and function - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Clinical Investigation Année : 2007

Prostate cell differentiation status determines transient receptor potential melastatin member 8 channel subcellular localization and function

Matthieu Flourakis
  • Fonction : Auteur
Stéphanie Thebault
  • Fonction : Auteur
Alexander Zholos
  • Fonction : Auteur
Benjamin Beck
  • Fonction : Auteur
Dimitra Gkika
Morad Roudbaraki
  • Fonction : Auteur
Jean-Louis Bonnal
  • Fonction : Auteur
Brigitte Mauroy
  • Fonction : Auteur
Yaroslav Shuba
  • Fonction : Auteur
Roman Skryma
  • Fonction : Auteur
Natalia Prevarskaya

Résumé

In recent years, the transient receptor potential melastatin member 8 (TRPM8) channel has emerged as a promising prognostic marker and putative therapeutic target in prostate cancer (PCa). However, the mechanisms of prostate-specific regulation and functional evolution of TRPM8 during PCa progression remain unclear. Here we show, for the first time to our knowledge, that only secretory mature differentiated human prostate primary epithelial (PrPE) luminal cells expressed functional plasma membrane TRPM8 (PM TRPM8) channels. Moreover, PCa epithelial cells obtained from in situ PCa were characterized by a significantly stronger PM TRPM8-mediated current than that in normal cells. This PM TRPM8 activity was abolished in dedifferentiated PrPE cells that had lost their luminal secretory phenotype. However, we found that in contrast to PM TRPM8, endoplasmic reticulum TRPM8 (ER TRPM8) retained its function as an ER Ca 2+ release channel, independent of cell differentiation. We hypothesize that the constitutive activity of ER TRPM8 may result from the expression of a truncated TRPM8 splice variant. Our study provides insight into the role of TRPM8 in PCa progression and suggests that TRPM8 is a potentially attractive target for therapeutic intervention: specific inhibition of either ER TRPM8 or PM TRPM8 may be useful, depending on the stage and androgen sensitivity of the targeted PCa.
Fichier principal
Vignette du fichier
prostate cell differentiation status determines TRPM8 channel subcellular localization and function.pdf (1.72 Mo) Télécharger le fichier
Origine Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-03060259 , version 1 (13-12-2020)

Licence

Identifiants

Citer

Gabriel Bidaux, Matthieu Flourakis, Stéphanie Thebault, Alexander Zholos, Benjamin Beck, et al.. Prostate cell differentiation status determines transient receptor potential melastatin member 8 channel subcellular localization and function. Journal of Clinical Investigation, 2007, 117 (6), pp.1647-1657. ⟨10.1172/JCI30168⟩. ⟨hal-03060259⟩
15 Consultations
32 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More