Prostaglandin E2 increases migration and proliferation of human glioblastoma cells by activating transient receptor potential melastatin 7 channels

Recent studies showed that both prostaglandin E2 ( PGE 2) and transient receptor potential melastatin 7 ( TRPM 7) play important roles in migration and proliferation of human glioblastoma cells. In this study, we tested the association between PGE 2 and TRPM 7. We found that PGE 2 increased TRPM 7 currents in HEK 293 and human glioblastoma A172 cells. The PGE 2 EP 3 receptor antagonist L‐798106 abrogated the PGE 2 stimulatory effect, while EP 3 agonist 17‐phenyl trinor prostaglandin E2 (17‐pt‐ PGE 2) mimicked the effect of PEG 2 on TRPM 7. The TRPM 7 phosphotransferase activity‐deficient mutation, K1646R had no effect on PGE 2 induced increase of TRPM 7 currents. Inhibition of protein kinase A ( PKA ) activity by Rp‐ cAMP increased TRPM 7 currents. TRPM 7 PKA phosphorylation site mutation S1269A abolished the PGE 2 effect on TRPM 7 currents. PGE 2 increased both mRNA and membrane protein expression of TRPM 7 in A172 cells. Knockdown of TRPM 7 by sh RNA abrogated the PGE 2 stimulated migration and proliferation of A172 cells. Blockage of TRPM 7 with 2‐aminoethoxydiphenyl borate (2‐ APB ) or NS 8593 had a similar effect as TRPM 7‐sh RNA . In conclusion, our results demonstrate that PGE 2 activates TRPM 7 via EP 3/ PKA signalling pathway, and that PGE 2 enhances migration and proliferation of human glioblastoma cells by up‐regulation of the TRPM 7 channel.