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

Acta Biochim Biophys Sin (Shanghai). 2016 Jan;48(1):75-81. doi: 10.1093/abbs/gmv115. Epub 2015 Nov 2.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Cell Movement
  • Cell Proliferation
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • GTP Phosphohydrolases / metabolism
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Humans
  • Immunotherapy / methods
  • Mice
  • Neoplasm Metastasis
  • Neoplasms / metabolism*
  • Signal Transduction

Substances

  • Guanine Nucleotide Exchange Factors
  • RAPGEF3 protein, human
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • GTP Phosphohydrolases