Insights into exchange factor directly activated by cAMP (EPAC) as potential target for cancer treatment

Mol Cell Biochem. 2018 Oct;447(1-2):77-92. doi: 10.1007/s11010-018-3294-z. Epub 2018 Feb 7.

Abstract

Cancer remains a global health problem and approximately 1.7 million new cancer cases are diagnosed every year worldwide. Although diverse molecules are currently being explored as targets for cancer therapy the tumor treatment and therapy is highly tricky. Secondary messengers are important for hormone-mediated signaling pathway. Cyclic AMP (cAMP), a secondary messenger responsible for various physiological processes regulates cell metabolism by activating Protein kinase A (PKA) and by targeting exchange protein directly activated by cAMP (EPAC). EPAC is present in two isoforms EPAC1 and EPAC2, which exhibit different tissue distribution and is involved in GDP/GTP exchange along with activating Rap1- and Rap2-mediated signaling pathways. EPAC is also known for its dual role in cancer as pro- and anti-proliferative in addition to metastasis. Results after perturbing EPAC activity suggests its involvement in cancer cell migration, proliferation, and cytoskeleton remodeling which makes it a potential therapeutic target for cancer treatments.

Keywords: Brain cancer; Breast cancer therapy; EPAC; Leukemia; Melanoma; Metastasis; Ovarian cancer; cAMP signaling.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Movement
  • Cell Proliferation
  • Cyclic AMP / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Humans
  • Neoplasm Proteins / metabolism*
  • Neoplasms* / metabolism
  • Neoplasms* / pathology
  • Neoplasms* / therapy
  • Second Messenger Systems*
  • Shelterin Complex
  • Telomere-Binding Proteins / metabolism
  • rap GTP-Binding Proteins / metabolism

Substances

  • Guanine Nucleotide Exchange Factors
  • Neoplasm Proteins
  • RAPGEF3 protein, human
  • RAPGEF4 protein, human
  • Shelterin Complex
  • TERF2IP protein, human
  • Telomere-Binding Proteins
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • RAP2A protein, human
  • rap GTP-Binding Proteins