cAMP inhibits migration, ruffling and paxillin accumulation in focal adhesions of pancreatic ductal adenocarcinoma cells: effects of PKA and EPAC

Biochim Biophys Acta. 2013 Dec;1833(12):2664-2672. doi: 10.1016/j.bbamcr.2013.06.011. Epub 2013 Jun 22.


We demonstrated that increasing intracellular cAMP concentrations result in the inhibition of migration of PANC-1 and other pancreatic ductal adenocarcinoma (PDAC) cell types. The rise of cAMP was accompanied by rapid and reversible cessation of ruffling, by inhibition of focal adhesion turnover and by prominent loss of paxillin from focal adhesions. All these phenomena develop rapidly suggesting that cAMP effectors have a direct influence on the cellular migratory apparatus. The role of two primary cAMP effectors, exchange protein activated by cAMP (EPAC) and protein kinase A (PKA), in cAMP-mediated inhibition of PDAC cell migration and migration-associated processes was investigated. Experiments with selective activators of EPAC and PKA demonstrated that the inhibitory effect of cAMP on migration, ruffling, focal adhesion dynamics and paxillin localisation is mediated by PKA, whilst EPAC potentiates migration.

Keywords: 3-isobutyl-1-methylxanthine; 6Bnz-cAMP; 8, 8-(4-chlorophenylthio)-2′-O-methyl-cAMP; 8, 8-bromoadenosine-cAMP; 8Br-cAMP; 8pCPT; A-kinase activity reporter four; AKAR4; CFP(nd)-EPAC(dDEP/CD)-Venus(d); Cell migration; DMEM; Dulbecco's modified Eagle's medium; EPAC; FBS; Frsk; H84; IBMX; N6-benzoyl-cAMP; PBS; PDAC; PKA; Pancreatic ductal adenocarcinoma; Paxillin; cAMP; exchange protein activated by cAMP; foetal bovine serum; forskolin; pancreatic ductal adenocarcinoma; phosphate buffered solution; protein kinase A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Adenocarcinoma / enzymology
  • Adenocarcinoma / pathology
  • Carcinoma, Pancreatic Ductal / enzymology
  • Carcinoma, Pancreatic Ductal / pathology*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Surface Extensions / drug effects
  • Cell Surface Extensions / metabolism*
  • Colforsin / pharmacology
  • Cyclic AMP / pharmacology*
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Focal Adhesions / drug effects
  • Focal Adhesions / metabolism*
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Humans
  • Neoplasm Invasiveness
  • Pancreatic Neoplasms / enzymology
  • Pancreatic Neoplasms / pathology
  • Paxillin / metabolism*
  • Protein Transport / drug effects


  • Guanine Nucleotide Exchange Factors
  • Paxillin
  • RAPGEF3 protein, human
  • Colforsin
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • 1-Methyl-3-isobutylxanthine