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Schematic diagram of the signaling pathways involved in NK1R-mediated MMPs up-regulation and cell migration in U-251 MG cells. hHK-1 binds to NK1R inducing Gq-mediated intracellular calcium release but has no effect on cAMP level. Phosphorylation of ERK, JNK, and Akt enhances AP-1 and/or NF-κB activity, resulting in the up-regulation of MMP-2 and MT1-MMP and glioma cell migration, as demonstrated by specific inhibitors, respectively.
