Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2014 Sep 16;111(37):E3870-9. doi: 10.1073/pnas.1413409111. Epub 2014 Aug 29.

TRPV6 calcium channel translocates to the plasma membrane via Orai1-mediated mechanism and controls cancer cell survival.

Author information

1
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;
2
Department of Cell Pathology, Catholic Institute of Lille, University of Lille Nord de France, St. Vincent Hospital, 59020 Lille, France;
3
Institute for Biophysics, Johannes Kepler Universität, A-4040 Linz, Austria; and.
4
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.
5
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.

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.

PMID:
25172921
PMCID:
PMC4169956
DOI:
10.1073/pnas.1413409111
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center