Figure 6.

β₂AR activates a positive feedforward cAMP/Ca²⁺ loop in MDA-MB-231HM cells to increase invasion. Upon agonist binding to β₂AR, Gα_s activates AC, which stimulates cAMP production. In highly metastatic breast cancer cells, Gβγ subunits activate Ca²⁺ mobilization, which is further increased by cAMP effector proteins PKA and Epac. This increase in Ca²⁺ feeds back to further stimulate cAMP production. Activation of the positive feedforward cAMP/Ca²⁺ loop identified in MDA-MB-231HM cells results in inhibition of pERK1/2 and independently accelerates breast cancer cell invasion.