cAMP inhibits migration,ruffling and paxillin accumulation in focal adhesions of pancreatic ductal adenocarcinoma cells: Effects of PKA and EPAC |
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| Authors: | Alex Burdyga Alan Conant Lee Haynes Jin Zhang Kees Jalink Robert Sutton John Neoptolemos Eithne Costello Alexei Tepikin |
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| Institution: | 1. Department of Cellular and Molecular Physiology, The University of Liverpool, Crown Street, Liverpool L69 3BX, UK;2. The Johns Hopkins University School of Medicine, Department of Neuroscience, 725 North Wolfe Street, Baltimore, MD 21205, USA;3. The Netherlands Cancer Institute, Cell Biology I, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands;4. NIHR Liverpool Pancreas Biomedical Research Unit, The University of Liverpool, Crown Street, Liverpool L69 3BX, UK;5. Department of Molecular and Clinical Cancer Medicine, 6th Floor, Duncan Building, Daulby Street, Liverpool, L69 3GA, UK |
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| Abstract: | 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. |
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