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 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.