TRPV6 channel controls prostate cancer cell proliferation via Ca(2+)/NFAT-dependent pathways.
The transient receptor potential channel, subfamily V, member 6 (TRPV6), is strongly expressed in advanced prostate cancer and significantly correlates with the Gleason >7 grading, being undetectable in healthy and benign prostate tissues. However, the role of TRPV6 as a highly Ca(2+)-selective channel in prostate carcinogenesis remains poorly understood. Here, we report that TRPV6 is directly involved in the control of prostate cancer cell (LNCaP cell line) proliferation by decreasing: (i) proliferation rate; (ii) cell accumulation in the S-phase of cell cycle and (iii) proliferating cell nuclear antigen (PCNA) expression. We demonstrate that the Ca(2+) uptake into LNCaP cells is mediated by TRPV6, with the subsequent downstream activation of the nuclear factor of activated T-cell transcription factor (NFAT). TRPV6-mediated Ca(2+) entry is also involved in apoptosis resistance of LNCaP cells. Our results suggest that TRPV6 expression in LNCaP cells is regulated by androgen receptor, however, in a ligand-independent manner. We conclude that the upregulation of TRPV6 Ca(2+) channel in prostate cancer cells may represent a mechanism for maintaining a higher proliferation rate, increasing cell survival and apoptosis resistance as well.
Lehen'kyi
V
V
Inserm, U-800, Equipe labellisée par la Ligue Nationale contre le cancer, Villeneuve d'Ascq, France.
Flourakis
M
M
Skryma
R
R
Prevarskaya
N
N
D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling; D049109:Cell Proliferation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008297:Male; D050778:NFATC Transcription Factors / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D016196:S Phase / Q000502:physiology; D015398:Signal Transduction; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D015220:Calcium Channels; D004791:Enzyme Inhibitors; D050778:NFATC Transcription Factors; D050916:TRPV Cation Channels; C422827:TRPV6 protein, human; D019284:Thapsigargin; D002118:Calcium