Figure 7.

Model of melatonin regulation of breast cancer cell invasion. Ligand-dependent activation of the membrane-associated G-protein-coupled receptor MT1 leads to coupling of G_i2 protein to MT1 receptor. As a result, the Gα_i2 subunit dissociates from the Gβγ subunits and inhibits the activity of adenylcyclase (AC), and this leads to a decrease in the intracellular level of cAMP and inhibition of protein kinase A (PKA) activity. The cAMP/PKA pathway cross-talks with the p38 pathway through PKA. In response to the reduced cAMP level, activity of p38 is suppressed, and this causes further downregulation of MMP-9 expression via repression of ETS1 transcriptional activity and, potentially, downregulation of MMP-2 transcription. MMP, matrix metalloproteinase.