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

Alex Burdyga; Alan Conant; Lee Haynes; Jin Zhang; Kees Jalink; Robert Sutton; John Neoptolemos; Eithne Costello; Alexei Tepikin

doi:10.1016/j.bbamcr.2013.06.011

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

Alex Burdyga, Alan Conant, Lee Haynes, Jin Zhang, Kees Jalink, Robert Sutton, John Neoptolemos, Eithne Costello, Alexei Tepikin

School of Medicine

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

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.

Original language	English (US)
Pages (from-to)	2664-2672
Number of pages	9
Journal	Biochimica et Biophysica Acta - Molecular Cell Research
Volume	1833
Issue number	12
DOIs	https://doi.org/10.1016/j.bbamcr.2013.06.011
State	Published - Dec 2013

Keywords

CAMP
Cell migration
EPAC
Pancreatic ductal adenocarcinoma
Paxillin
PKA

ASJC Scopus subject areas

Cell Biology
Molecular Biology

Access to Document

10.1016/j.bbamcr.2013.06.011

Cite this

Burdyga, A., Conant, A., Haynes, L., Zhang, J., Jalink, K., Sutton, R., Neoptolemos, J., Costello, E., & Tepikin, A. (2013). CAMP inhibits migration, ruffling and paxillin accumulation in focal adhesions of pancreatic ductal adenocarcinoma cells: Effects of PKA and EPAC. Biochimica et Biophysica Acta - Molecular Cell Research, 1833(12), 2664-2672. https://doi.org/10.1016/j.bbamcr.2013.06.011

Burdyga, A, Conant, A, Haynes, L, Zhang, J, Jalink, K, Sutton, R, Neoptolemos, J, Costello, E & Tepikin, A 2013, 'CAMP inhibits migration, ruffling and paxillin accumulation in focal adhesions of pancreatic ductal adenocarcinoma cells: Effects of PKA and EPAC', Biochimica et Biophysica Acta - Molecular Cell Research, vol. 1833, no. 12, pp. 2664-2672. https://doi.org/10.1016/j.bbamcr.2013.06.011

@article{f597f0b0d91a41c4ba37c52157aded88,

title = "CAMP inhibits migration, ruffling and paxillin accumulation in focal adhesions of pancreatic ductal adenocarcinoma cells: Effects of PKA and EPAC",

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.",

keywords = "CAMP, Cell migration, EPAC, Pancreatic ductal adenocarcinoma, Paxillin, PKA",

author = "Alex Burdyga and Alan Conant and Lee Haynes and Jin Zhang and Kees Jalink and Robert Sutton and John Neoptolemos and Eithne Costello and Alexei Tepikin",

year = "2013",

month = dec,

doi = "10.1016/j.bbamcr.2013.06.011",

language = "English (US)",

volume = "1833",

pages = "2664--2672",

journal = "Biochimica et Biophysica Acta - Molecular Cell Research",

issn = "0167-4889",

publisher = "Elsevier B.V.",

number = "12",

}

TY - JOUR

T1 - CAMP inhibits migration, ruffling and paxillin accumulation in focal adhesions of pancreatic ductal adenocarcinoma cells

T2 - Effects of PKA and EPAC

AU - Burdyga, Alex

AU - Conant, Alan

AU - Haynes, Lee

AU - Zhang, Jin

AU - Jalink, Kees

AU - Sutton, Robert

AU - Neoptolemos, John

AU - Costello, Eithne

AU - Tepikin, Alexei

PY - 2013/12

Y1 - 2013/12

N2 - 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.

AB - 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.

KW - CAMP

KW - Cell migration

KW - EPAC

KW - Pancreatic ductal adenocarcinoma

KW - Paxillin

KW - PKA

UR - http://www.scopus.com/inward/record.url?scp=84882579435&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84882579435&partnerID=8YFLogxK

U2 - 10.1016/j.bbamcr.2013.06.011

DO - 10.1016/j.bbamcr.2013.06.011

M3 - Article

C2 - 23797058

AN - SCOPUS:84882579435

SN - 0167-4889

VL - 1833

SP - 2664

EP - 2672

JO - Biochimica et Biophysica Acta - Molecular Cell Research

JF - Biochimica et Biophysica Acta - Molecular Cell Research

IS - 12

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this