title: Targeting of short TRPM8 isoforms induces 4TM-TRPM8-dependent apoptosis in prostate cancer cells.
abstract: Since its cloning a decade ago, TRPM8 channel has emerged as a promising prognostic marker and a putative therapeutic target in prostate cancer (PCa). However, recent studies have brought to light the complexity of TRPM8 isoforms in PCa. Consequently, the respective role of each TRPM8 isoform needs to be deciphered prior to considering TRPM8 as an attractive therapeutic target. Full-length (6 transmembrane (TM)-domain) TRPM8 channel is overexpressed in early PCa and repressed in advanced prostate tumors whereas the localization of the truncated, 4TM-TRPM8 channel (4 transmembrane (TM)-domain), in the membranes of endoplasmic reticulum (ER) is independent of the pathogenic status of epithelial cells. In the same line, expression of non-channel cytoplasmic small TRPM8 isoforms (namely sM8) is conserved in cancer cells. In this study, we identify sM8s as putative regulator of PCa cell death. Indeed, suppression of sM8 isoforms was found to induce concomitantly ER stress, oxidative stress, p21 expression and apoptosis in human epithelial prostate cancer cells. We furthermore demonstrate that induction of such mechanisms required the activity of 4TM-TRPM8 channels at the ER-mitochondria junction. Our study thus suggests that targeting sM8 could be an appropriate strategy to fight prostate cancer.
authors.affiliation: Inserm, U-1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villeneuve d'Ascq, France.|Université des Sciences et Technologies de Lille (USTL), Villeneuve d'Ascq, France.|Laboratoire de Physique des Lasers, Atomes and Molécules, Equipe Biophotonique Cellulaire Fonctionnelle, Parc Scientifique de la Haute Borne, Villeneuve d'Ascq, France.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Bidaux
authors.affiliation: Inserm, U-1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villeneuve d'Ascq, France.|Université des Sciences et Technologies de Lille (USTL), Villeneuve d'Ascq, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Borowiec
authors.affiliation: Inserm, U-1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villeneuve d'Ascq, France.|Université des Sciences et Technologies de Lille (USTL), Villeneuve d'Ascq, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Dubois
authors.affiliation: Inserm, U-1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villeneuve d'Ascq, France.|Université des Sciences et Technologies de Lille (USTL), Villeneuve d'Ascq, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Delcourt
authors.affiliation: Inserm, U-1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villeneuve d'Ascq, France.|Université des Sciences et Technologies de Lille (USTL), Villeneuve d'Ascq, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Schulz
authors.affiliation: Inserm, U-1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villeneuve d'Ascq, France.|Université des Sciences et Technologies de Lille (USTL), Villeneuve d'Ascq, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Vanden Abeele
authors.affiliation: Inserm, U-1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villeneuve d'Ascq, France.|Université des Sciences et Technologies de Lille (USTL), Villeneuve d'Ascq, France.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Lepage
authors.affiliation: Inserm, U-1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villeneuve d'Ascq, France.|Université des Sciences et Technologies de Lille (USTL), Villeneuve d'Ascq, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Desruelles
authors.affiliation: Inserm, U-1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villeneuve d'Ascq, France.|Université des Sciences et Technologies de Lille (USTL), Villeneuve d'Ascq, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bokhobza
authors.affiliation: Inserm, U-1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villeneuve d'Ascq, France.|Université des Sciences et Technologies de Lille (USTL), Villeneuve d'Ascq, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Dewailly
authors.affiliation: Inserm, U-1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villeneuve d'Ascq, France.|Université des Sciences et Technologies de Lille (USTL), Villeneuve d'Ascq, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Slomianny
authors.affiliation: Inserm, U-1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villeneuve d'Ascq, France.|Université des Sciences et Technologies de Lille (USTL), Villeneuve d'Ascq, France.
authors.forename: Morad
authors.initials: M
authors.lastname: Roudbaraki
authors.affiliation: Laboratoire de Physique des Lasers, Atomes and Molécules, Equipe Biophotonique Cellulaire Fonctionnelle, Parc Scientifique de la Haute Borne, Villeneuve d'Ascq, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Héliot
authors.affiliation: Inserm, U-1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villeneuve d'Ascq, France.|Université des Sciences et Technologies de Lille (USTL), Villeneuve d'Ascq, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Bonnal
authors.affiliation: Inserm, U-1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villeneuve d'Ascq, France.|Université des Sciences et Technologies de Lille (USTL), Villeneuve d'Ascq, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Mauroy
authors.affiliation: Inserm, U-1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villeneuve d'Ascq, France.|Université des Sciences et Technologies de Lille (USTL), Villeneuve d'Ascq, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Mariot
authors.affiliation: Inserm, U-1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villeneuve d'Ascq, France.|Université des Sciences et Technologies de Lille (USTL), Villeneuve d'Ascq, France.
authors.forename: Loïc
authors.initials: L
authors.lastname: Lemonnier
authors.affiliation: Inserm, U-1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Villeneuve d'Ascq, France.|Université des Sciences et Technologies de Lille (USTL), Villeneuve d'Ascq, France.
authors.forename: Natalia
authors.initials: N
authors.lastname: Prevarskaya
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D020033:Protein Isoforms / Q000378:metabolism; D050053:TRPM Cation Channels / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D050053:TRPM Cation Channels; C425966:TRPM8 protein, human
keywords: ER calcium fluxes; TRPM8; apoptosis; mitochondria; prostate cancer