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.External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c

Raphael, M., Lehen'kyi, V., Vandenberghe, M., Beck, B., Khalimonchyk, S., Vanden Abeele, F., Farsetti, L., Germain, E., Bokhobza, A., Mihalache, A., Gosset, P., Romanin, C., Clezardin, P., Skryma, R., Prevarskaya, N.,
["Institut National de la Sante et de la Recherche Medicale U1003, Equipe Labellisee par la Ligue Nationale Contre le Cancer, Laboratory of Excellence Ion Channel Science and Therapeutics, Universite des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France;", "Institut National de la Sante et de la Recherche Medicale U1003, Equipe Labellisee par la Ligue Nationale Contre le Cancer, Laboratory of Excellence Ion Channel Science and Therapeutics, Universite des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France;", "Institut National de la Sante et de la Recherche Medicale U1003, Equipe Labellisee par la Ligue Nationale Contre le Cancer, Laboratory of Excellence Ion Channel Science and Therapeutics, Universite des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France;", "Institut National de la Sante et de la Recherche Medicale U1003, Equipe Labellisee par la Ligue Nationale Contre le Cancer, Laboratory of Excellence Ion Channel Science and Therapeutics, Universite des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France;", "Institut National de la Sante et de la Recherche Medicale U1003, Equipe Labellisee par la Ligue Nationale Contre le Cancer, Laboratory of Excellence Ion Channel Science and Therapeutics, Universite des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France;", "Institut National de la Sante et de la Recherche Medicale U1003, Equipe Labellisee par la Ligue Nationale Contre le Cancer, Laboratory of Excellence Ion Channel Science and Therapeutics, Universite des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France;", "Institut National de la Sante et de la Recherche Medicale U1003, Equipe Labellisee par la Ligue Nationale Contre le Cancer, Laboratory of Excellence Ion Channel Science and Therapeutics, Universite des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France;", "Institut National de la Sante et de la Recherche Medicale U1003, Equipe Labellisee par la Ligue Nationale Contre le Cancer, Laboratory of Excellence Ion Channel Science and Therapeutics, Universite des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France;", "Institut National de la Sante et de la Recherche Medicale U1003, Equipe Labellisee par la Ligue Nationale Contre le Cancer, Laboratory of Excellence Ion Channel Science and Therapeutics, Universite des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France;", "Department of Cell Pathology, Catholic Institute of Lille, University of Lille Nord de France, St. Vincent Hospital, 59020 Lille, France;", "Department of Cell Pathology, Catholic Institute of Lille, University of Lille Nord de France, St. Vincent Hospital, 59020 Lille, France;", "Institute for Biophysics, Johannes Kepler Universitat, A-4040 Linz, Austria; and.", "Institut National de la Sante et de la Recherche Medicale Unite Mixte de Recherche 1033, Faculty of Medicine Lyon-Est, 69372 Lyon Cedex 08, France.", "Institut National de la Sante et de la Recherche Medicale U1003, Equipe Labellisee par la Ligue Nationale Contre le Cancer, Laboratory of Excellence Ion Channel Science and Therapeutics, Universite des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France;", "Institut National de la Sante et de la Recherche Medicale U1003, Equipe Labellisee par la Ligue Nationale Contre le Cancer, Laboratory of Excellence Ion Channel Science and Therapeutics, Universite des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq, France; Natacha.Prevarskaya@univ-lille1.fr."]
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: 25172921External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c
Validation: In vivo validation Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Assay with endogenous proteins Assay with overexpressed proteins Reference
Cell or tissue Cell or tissue TRP channel construct Interactor construct
TRP channel Interactor Method Species Region Species Region
TRPC1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 TRPV6 Co-immunoprecipitation LNCaP 25172921
TRPV6 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 TRPC1 Co-immunoprecipitation LNCaP 25172921
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

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