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2018 ; 22
(12
): 6327-6337
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Prostaglandin E2 increases migration and proliferation of human glioblastoma
cells by activating transient receptor potential melastatin 7 channels
#MMPMID30338939
Tian Y
; Yang T
; Yu S
; Liu C
; He M
; Hu C
J Cell Mol Med
2018[Dec]; 22
(12
): 6327-6337
PMID30338939
show ga
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.
|Cell Line, Tumor
[MESH]
|Cell Movement/genetics
[MESH]
|Cell Proliferation/genetics
[MESH]
|Cyclic AMP-Dependent Protein Kinases/genetics
[MESH]