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Review
. 2020 Nov 24;9(1):32.
doi: 10.1186/s40164-020-00191-1.

Complex roles of cAMP-PKA-CREB signaling in cancer

Hongying Zhang  1 , Qingbin Kong  1 , Jiao Wang  2 , Yangfu Jiang  1 , Hui Hua  3
Affiliations
Review

Complex roles of cAMP-PKA-CREB signaling in cancer

Hongying Zhang et al. Exp Hematol Oncol. .

Abstract

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.

Keywords: CREB; Cancer; PKA; cAMP.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
cAMP signaling pathway. The generation of cAMP is regulated in a G-protein dependent manner by AC or G-protein independent manner by sAC. The degradation of cAMP is regulated by PDEs. cAMP can regulate multiple signaling pathways including ion channes, Epac, and PKA. R the regulatory subunit of PKA, C the catalytic subunit of PKA
Fig. 2
Fig. 2
The domains of CREB family proteins. The CREB family proteins contain a kinase inducible domain (KID), two glutamate domains (Q1 and Q2), and a basic leucine zipper domain (bZIP)
Fig. 3
Fig. 3
Cell signaling pathways for activating CREB/ATF1. CREB/ATF1 can be phosphorylated by multiple kinases including Akt, RSK, MSK, PKA, CAMKII and CAMKIV
See this image and copyright information in PMC

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