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

par Raphaël, Maylis;Lehen'kyi, V'yacheslav;Vandenberghe, Matthieu;Beck, Benjamin ;Khalimonchyk, Sergiy;Vanden Abeele, Fabien;Farsetti, Leonardo;Germain, Emmanuelle;Bokhobza, Alexandre;Skryma, Roman;Prevarskaya, Natalia;Mihalache, Adriana;Gosset, Pierre;Romanin, Christoph;Clezardin, Philippe
Référence Proceedings of the National Academy of Sciences of the United States of America, 111, 37, page (E3870-E3879)
Publication Publié, 2014-09

Article révisé par les pairs

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Résumé :

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 Ca2+/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 Ca2+/Annexin I/S100A11 pathway.