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

Abstract

Recent studies showed that both prostaglandin E2 (PGE2) and transient receptor potential melastatin 7 (TRPM7) play important roles in migration and proliferation of human glioblastoma cells. In this study, we tested the association between PGE2 and TRPM7. We found that PGE2 increased TRPM7 currents in HEK293 and human glioblastoma A172 cells. The PGE2 EP3 receptor antagonist L‐798106 abrogated the PGE2 stimulatory effect, while EP3 agonist 17‐phenyl trinor prostaglandin E2 (17‐pt‐PGE2) mimicked the effect of PEG2 on TRPM7. The TRPM7 phosphotransferase activity‐deficient mutation, K1646R had no effect on PGE2 induced increase of TRPM7 currents. Inhibition of protein kinase A (PKA) activity by Rp‐cAMP increased TRPM7 currents. TRPM7 PKA phosphorylation site mutation S1269A abolished the PGE2 effect on TRPM7 currents. PGE2 increased both mRNA and membrane protein expression of TRPM7 in A172 cells. Knockdown of TRPM7 by shRNA abrogated the PGE2 stimulated migration and proliferation of A172 cells. Blockage of TRPM7 with 2‐aminoethoxydiphenyl borate (2‐APB) or NS8593 had a similar effect as TRPM7‐shRNA. In conclusion, our results demonstrate that PGE2 activates TRPM7 via EP3/PKA signalling pathway, and that PGE2 enhances migration and proliferation of human glioblastoma cells by up‐regulation of the TRPM7 channel.

Mapping TRPM7 Function by NS8593

“…Prostaglandin E2 (PGE2) plays a role in the migration and proliferation of human glioblastoma cells [ 111 ]. Tian et al [ 111 ] observed that PGE2 increased TRPM7 currents in human glioblastoma A172 cells.…”

“…Prostaglandin E2 (PGE2) plays a role in the migration and proliferation of human glioblastoma cells [ 111 ]. Tian et al [ 111 ] observed that PGE2 increased TRPM7 currents in human glioblastoma A172 cells. Knockdown of TRPM7 by shRNA or exposure of cells to NS8593 abrogated PGE2-stimulated motility and proliferation of A172 cells [ 111 ].…”

“…Tian et al [ 111 ] observed that PGE2 increased TRPM7 currents in human glioblastoma A172 cells. Knockdown of TRPM7 by shRNA or exposure of cells to NS8593 abrogated PGE2-stimulated motility and proliferation of A172 cells [ 111 ]. Zou et al [ 114 ] used NS8593 as one of the tools to establish an interplay between TRPM7 and epidermal growth factor receptor (EGFR) signalling in vascular smooth muscle (VSMC) cells.…”

Advances in research on the active constituents and physiological effects of Ganoderma lucidum

“…FYGL has dose-dependent hypoglycemic and hypolipidemic effects and could increase blood insulin levels. Furthermore, it inhibited the overexpression of PTP1B, enhanced insulin-stimulated glycogen synthesis, and decreased blood glucose in a mouse model of insulin resistance (Tian et al 2018). FYGL can ameliorate type 2 diabetes mellitus caused by mitochondrial dysfunction and can decrease ROS level (Yang et al 2019).…”

“…Modern pharmacology has shown that G. lucidum has antitumor (Kao et al 2016), anti-inflammatory (Liu et al 2018), and antioxidation effects (Sarnthima et al 2017) and that it could regulate the respiratory, nervous, and immune systems (Kubota et al 2018). G. lucidum also has a hypoglycemic effect (Tian et al 2018) and can protect the liver (Wu et al 2016). Nowadays, G. lucidum is used as a powder, tea, and dietary supplement.…”