Differential role of transient receptor potential channels in Ca2+ entry and proliferation of prostate cancer epithelial cells.. Differential role of transient receptor potential channels in Ca2+ entry and proliferation of prostate cancer epithelial cells.: Role of TRP Channels in Proliferation

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Thebault, Stephanie | Flourakis, Matthieu | Vanoverberghe, Karine | Vandermoere, Franck | Roudbaraki, Morad | Lehen'Kyi, V'Yacheslav | Slomianny, Christian | Beck, Benjamin | Mariot, Pascal | Bonnal, Jean-Louis | Mauroy, Brigitte | Shuba, Yaroslav | Capiod, Thierry | Skryma, Roman | Prevarskaya, Natalia

Edité par CCSD ; American Association for Cancer Research -

One major clinical problem with prostate cancer is the cells' ability to survive and proliferate upon androgen withdrawal. Because Ca2+ is central to growth control, understanding the mechanisms of Ca2+ homeostasis involved in prostate cancer cell proliferation is imperative for new therapeutic strategies. Here, we show that agonist-mediated stimulation of alpha1-adrenergic receptors (alpha1-AR) promotes proliferation of the primary human prostate cancer epithelial (hPCE) cells by inducing store-independent Ca2+ entry and subsequent activation of nuclear factor of activated T cells (NFAT) transcription factor. Such an agonist-induced Ca2+ entry (ACE) relied mostly on transient receptor potential canonical 6 (TRPC6) channels, whose silencing by antisense hybrid depletion decreased both hPCE cell proliferation and ACE. In contrast, ACE and related growth arrest associated with purinergic receptors (P2Y-R) stimulation involved neither TRPC6 nor NFAT. Our findings show that alpha1-AR signaling requires the coupled activation of TRPC6 channels and NFAT to promote proliferation of hPCE cells and thereby suggest TRPC6 as a novel potential therapeutic target.

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