cAMP effects in neuroendocrine tumors: The role of Epac and PKA in cell proliferation and adhesion

cAMP effects have been initially attributed to protein kinase A (PKA) activation. Subsequently, two exchange proteins directly activated by cAMP (Epac1/2) have been identified as cAMP targets. Aim of this study was to investigate cAMP effects in pancreatic-NET (P-NET) and bronchial carcinoids and in corresponding cell lines (QGP-1 and H727) on cell proliferation and adhesion and to determine PKA and Epac role in mediating these effects. We found that cAMP increased cyclin D1 expression in P-NET and QGP-1 cells, whereas it had opposite effects on bronchial carcinoids and H727 cells and it promoted cell adhesion in QGP-1 and H727 cells. These effects are mimicked by Epac and PKA specific analogs, activating the small GTPase Rap1. In conclusion, we demonstrated that cAMP exerted divergent effects on proliferation and promoted cell adhesion of different neuroendocrine cell types, these effects being mediated by both Epac and PKA and involving the same effector GTPase Rap1. •cAMP increased and decreased cell proliferation in different neuroendocrine cells.•cAMP divergent effects on proliferation are mimicked by both Epac and PKA.•cAMP and its effectors promoted cell adhesion in neuroendocrine tumor cells.•Epac and PKA act through the activation of same effector, Ras-like GTP-ase Rap1.