Complex roles of cAMP–PKA–CREB signaling in cancer

Cyclic adenosine monophosphate (cAMP) is the first discovered second messenger, which plays pivotal roles in cell signaling, and regulates many physiological and pathological processes. cAMP can regulate the transcription of various target genes, mainly through protein kinase A (PKA) and its downstream effectors such as cAMP-responsive element binding protein (CREB). In addition, PKA can phosphorylate many kinases such as Raf, GSK3 and FAK. Aberrant cAMP-PKA signaling is involved in various types of human tumors. Especially, cAMP signaling may have both tumor-suppressive and tumor-promoting roles depending on the tumor types and context. cAMP-PKA signaling can regulate cancer cell growth, migration, invasion and metabolism. This review highlights the important roles of cAMP-PKA-CREB signaling in tumorigenesis. The potential strategies to target this pathway for cancer therapy are also discussed.