RT Journal Article
SR Electronic
T1 A Novel EPAC-Specific Inhibitor Suppresses Pancreatic Cancer Cell Migration and Invasion
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 122
OP 128
DO 10.1124/mol.112.080689
VO 83
IS 1
A1 Muayad Almahariq
A1 Tamara Tsalkova
A1 Fang C. Mei
A1 Haijun Chen
A1 Jia Zhou
A1 Sarita K. Sastry
A1 Frank Schwede
A1 Xiaodong Cheng
YR 2013
UL http://molpharm.aspetjournals.org/content/83/1/122.abstract
AB Exchange protein directly activated by cAMP (EPAC) and cAMP-dependent protein kinase (PKA) are two intracellular receptors that mediate the effects of the prototypic second messenger cAMP. Identifying pharmacological probes for selectively modulating EPAC activity represents a significant unmet need within the research field. Herein, we report the identification and characterization of 3-(5-tert-butyl-isoxazol-3-yl)-2-[(3-chloro-phenyl)-hydrazono]-3-oxo-propionitrile (ESI-09), a novel noncyclic nucleotide EPAC antagonist that is capable of specifically blocking intracellular EPAC-mediated Rap1 activation and Akt phosphorylation, as well as EPAC-mediated insulin secretion in pancreatic β cells. Using this novel EPAC-specific inhibitor, we have probed the functional roles of overexpression of EPAC1 in pancreatic cancer cells. Our studies show that EPAC1 plays an important role in pancreatic cancer cell migration and invasion, and thus represents a potential target for developing novel therapeutic strategies for pancreatic cancer.