CREB1 and non-small cell lung carcinoma: NNK is an agonist for nAChRs [7] as well as β-ARs [28], and in vitro studies with NSCLC cells and small airway epithelial cells have shown that beta-adrenergic receptor activation by a synthetic agonist or NNK activated the adenylyl cyclase/cAMP/PKA/CREB cascade while at the same time trans-activating EGFR and its downstream effectors in a PKA-dependent manner [27]–[29], [44].