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Review
. 2016 Jan;48(1):75-81.
doi: 10.1093/abbs/gmv115. Epub 2015 Nov 2.

The pleiotropic role of exchange protein directly activated by cAMP 1 (EPAC1) in cancer: implications for therapeutic intervention

Muayad Almahariq  1 , Fang C Mei  2 , Xiaodong Cheng  3
Affiliations
Review

The pleiotropic role of exchange protein directly activated by cAMP 1 (EPAC1) in cancer: implications for therapeutic intervention

Muayad Almahariq et al. Acta Biochim Biophys Sin (Shanghai). 2016 Jan.

Abstract

The pleiotropic second messenger adenosine 3',5'-cyclic monophosphate (cAMP) regulates a myriad of biological processes under both physiological and pathophysiological conditions. Exchange protein directly activated by cAMP 1 (EPAC1) mediates the intracellular functions of cAMP by acting as a guanine nucleotide exchange factor for the Ras-like Rap small GTPases. Recent studies suggest that EPAC1 plays important roles in immunomodulation, cancer cell migration/metastasis, and metabolism. These results, coupled with the successful development of EPAC-specific small molecule inhibitors, identify EPAC1 as a promising therapeutic target for cancer treatments.

Keywords: EPAC1; PKA; cancer cAMP; therapeutic target.

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Figures

Figure 1.
Figure 1.
Proposed model for the therapeutic potential of EPAC1 inhibitors in cancer treatment Inhibition of EPAC1 in tumor cells has the potential to reduce the oncogenic effects of up-regulated glucose metabolism and to inhibit invasion/migration of cancer cells. On the other hand, inhibition of EPAC1 in the normal host cells has the potential to down-regulate the activity of Treg and consequently boosts the anti-tumor activity of Teff. BM: basement membrane.
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References

    1. Beavo JA, Brunton LL. Cyclic nucleotide research—still expanding after half a century. Nat Rev Mol Cell Biol 2002, 3: 710–718. - PubMed
    1. Craven KB, Zagotta WN. CNG and HCN channels: two peas, one pod. Annu Rev Physiol 2006, 68: 375–401. - PubMed
    1. Kawasaki H, Springett GM, Mochizuki N, Toki S, Nakaya M, Matsuda M, Housman DE et al. . A family of cAMP-binding proteins that directly activate Rap1. Science 1998, 282: 2275–2279. - PubMed
    1. de Rooij J, Zwartkruis FJ, Verheijen MH, Cool RH, Nijman SM, Wittinghofer A, Bos JL. Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP. Nature 1998, 396: 474–477. - PubMed
    1. Rehmann H, Das J, Knipscheer P, Wittinghofer A, Bos JL. Structure of the cyclic-AMP-responsive exchange factor Epac2 in its auto-inhibited state. Nature 2006, 439: 625–628. - PubMed

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