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

Significance Transient receptor potential vanilloid subfamily member 6 (TRPV6) is a highly selective Ca ²⁺ channel that exercises its normal physiological function via Ca ²⁺ absorption in the intestine and kidney. Intriguingly, we show that the TRPV6 channel may switch from its well-known constituti...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 111; no. 37; pp. E3870 - E3879
Main Authors Raphaël, Maylis, Lehen'kyi, V'yacheslav, Vandenberghe, Matthieu, Beck, Benjamin, Khalimonchyk, Sergiy, Vanden Abeele, Fabien, Farsetti, Leonardo, Germain, Emmanuelle, Bokhobza, Alexandre, Mihalache, Adriana, Gosset, Pierre, Romanin, Christoph, Clézardin, Philippe, Skryma, Roman, Prevarskaya, Natalia
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 16.09.2014
National Acad Sciences
SeriesPNAS Plus
Subjects
Animals
Annexin A1 - metabolism
Apoptosis
Biological Sciences
Bone Neoplasms - diagnostic imaging
Bone Neoplasms - secondary
Calcium
Calcium - metabolism
Calcium Channels - metabolism
Cancer
Carcinogenesis - pathology
Cell Line, Tumor
Cell Membrane - metabolism
Cell Survival
Cells
Disease Progression
Endoplasmic Reticulum - metabolism
Gene expression
HEK293 Cells
Humans
Immunohistochemistry
Life Sciences
Male
Membranes
Mice, Nude
Neoplasm Invasiveness
Neoplasm Proteins - metabolism
ORAI1 Protein
Phenotype
Plasma
PNAS Plus
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - pathology
Protein Transport
Radiography
S100 Proteins - metabolism
Signal Transduction
TRPV Cation Channels - metabolism
Xenograft Model Antitumor Assays
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Summary:Significance Transient receptor potential vanilloid subfamily member 6 (TRPV6) is a highly selective Ca ²⁺ channel that exercises its normal physiological function via Ca ²⁺ absorption in the intestine and kidney. Intriguingly, we show that the TRPV6 channel may switch from its well-known constitutive activity to the store operated due to the remodeling mechanism involving STIM1/Orai1/TRPC1-induced activation of TRPV6 channel translocation to the plasma membrane via the Ca ²⁺/Annexin I/S100A11 pathway. Moreover, we demonstrate that the discovered mechanism is used by prostate cancer cells. This channel is absent in healthy prostate and is expressed de novo in prostate cancer cells, where it changes the role by supplying Ca ²⁺, which is used in cancer to increase cell survival.
Bibliography:http://dx.doi.org/10.1073/pnas.1413409111
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PMCID: PMC4169956
Author contributions: M.R., V.L., F.V.A., and N.P. designed research; V.L., P.G., C.R., P.C., and R.S. contributed new reagents/analytic tools; M.R., V.L., M.V., B.B., S.K., F.V.A., L.F., E.G., A.B., and A.M. performed research; M.R., V.L., M.V., B.B., S.K., F.V.A., L.F., E.G., A.M., P.G., C.R., P.C., and R.S. analyzed data; and V.L. and N.P. wrote the paper.
2V.L. and N.P. contributed equally to this work.
4Present address: Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, 1070 Bruxelles, Belgium.
1M.R., V.L., and M.V. contributed equally to this work.
Edited by Lutz Birnbaumer, National Institute of Environmental Health Sciences, Research Triangle Park, NC, and approved August 1, 2014 (received for review July 15, 2014)
3Present address: Department of Medicine, Dermatology Research, University of California, San Diego, La Jolla, CA 92121.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1413409111