Figure 3.

In NSCLC cells with EGFR activating mutations, activation of b2-ARs promotes resistance to EGFR tyrosine kinase inhibitors (TKIs) though an IL-6-dependent mechanism. Chronic stress hormones activate B2-ARs on lung cancer cells triggering activation of adenylyl cyclase and a rise in intracellular cAMP. This in turn activates protein kinase C (PKC), which phosphorylates CREB leading to increased transcription of CREB target genes including IL-6. PKC also phosphorylates the tumor suppressor LKB1 at the S428 inhibitory site, which results in increased mTOR signaling.