title: TRPV6 calcium channel translocates to the plasma membrane via Orai1-mediated mechanism and controls cancer cell survival.
abstract: Transient receptor potential vanilloid subfamily member 6 (TRPV6) is a highly selective calcium channel that has been considered as a part of store-operated calcium entry (SOCE). Despite its first discovery in the early 2000s, the role of this channel in prostate cancer (PCa) remained, until now, obscure. Here we show that TRPV6 mediates calcium entry, which is highly increased in PCa due to the remodeling mechanism involving the translocation of the TRPV6 channel to the plasma membrane via the Orai1/TRPC1-mediated Ca(2+)/Annexin I/S100A11 pathway, partially contributing to SOCE. The TRPV6 calcium channel is expressed de novo by the PCa cell to increase its survival by enhancing proliferation and conferring apoptosis resistance. Xenografts in nude mice and bone metastasis models confirmed the remarkable aggressiveness of TRPV6-overexpressing tumors. Immunohistochemical analysis of these demonstrated the increased expression of clinical markers such as Ki-67, prostate specific antigen, synaptophysin, CD31, and CD56, which are strongly associated with a poor prognosis. Thus, the TRPV6 channel acquires its oncogenic potential in PCa due to the remodeling mechanism via the Orai1-mediated Ca(2+)/Annexin I/S100A11 pathway.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Laboratory of Excellence Ion Channel Science and Therapeutics, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France;
authors.forename: Maylis
authors.initials: M
authors.lastname: Raphaël
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Laboratory of Excellence Ion Channel Science and Therapeutics, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France;
authors.forename: V'yacheslav
authors.initials: V
authors.lastname: Lehen'kyi
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Laboratory of Excellence Ion Channel Science and Therapeutics, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France;
authors.forename: Matthieu
authors.initials: M
authors.lastname: Vandenberghe
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Laboratory of Excellence Ion Channel Science and Therapeutics, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France;
authors.forename: Benjamin
authors.initials: B
authors.lastname: Beck
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Laboratory of Excellence Ion Channel Science and Therapeutics, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France;
authors.forename: Sergiy
authors.initials: S
authors.lastname: Khalimonchyk
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Laboratory of Excellence Ion Channel Science and Therapeutics, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France;
authors.forename: Fabien
authors.initials: F
authors.lastname: Vanden Abeele
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Laboratory of Excellence Ion Channel Science and Therapeutics, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France;
authors.forename: Leonardo
authors.initials: L
authors.lastname: Farsetti
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Laboratory of Excellence Ion Channel Science and Therapeutics, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France;
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Germain
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Laboratory of Excellence Ion Channel Science and Therapeutics, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France;
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bokhobza
authors.affiliation: Department of Cell Pathology, Catholic Institute of Lille, University of Lille Nord de France, St. Vincent Hospital, 59020 Lille, France;
authors.forename: Adriana
authors.initials: A
authors.lastname: Mihalache
authors.affiliation: Department of Cell Pathology, Catholic Institute of Lille, University of Lille Nord de France, St. Vincent Hospital, 59020 Lille, France;
authors.forename: Pierre
authors.initials: P
authors.lastname: Gosset
authors.affiliation: Institute for Biophysics, Johannes Kepler Universität, A-4040 Linz, Austria; and.
authors.forename: Christoph
authors.initials: C
authors.lastname: Romanin
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 1033, Faculty of Medicine Lyon-Est, 69372 Lyon Cedex 08, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Clézardin
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Laboratory of Excellence Ion Channel Science and Therapeutics, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France;
authors.forename: Roman
authors.initials: R
authors.lastname: Skryma
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Laboratory of Excellence Ion Channel Science and Therapeutics, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France; Natacha.Prevarskaya@univ-lille1.fr.
authors.forename: Natalia
authors.initials: N
authors.lastname: Prevarskaya
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000378:metabolism; D017209:Apoptosis; D001859:Bone Neoplasms / Q000000981:diagnostic imaging / Q000556:secondary; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D063646:Carcinogenesis / Q000473:pathology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D002470:Cell Survival; D018450:Disease Progression; D004721:Endoplasmic Reticulum / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D000071740:ORAI1 Protein; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D021381:Protein Transport; D011859:Radiography; D009418:S100 Proteins / Q000378:metabolism; D015398:Signal Transduction; D050916:TRPV Cation Channels / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D017305:Annexin A1; D015220:Calcium Channels; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D009418:S100 Proteins; D050916:TRPV Cation Channels; C422827:TRPV6 protein, human; C072337:S100A11 protein, human; D002118:Calcium