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dc.contributor.authorAnton, KA
dc.contributor.authorSinclair, J
dc.contributor.authorOhoka, A
dc.contributor.authorKajita, M
dc.contributor.authorIshikawa, S
dc.contributor.authorBenz, PM
dc.contributor.authorRenne, T
dc.contributor.authorBalda, M
dc.contributor.authorJorgensen, C
dc.contributor.authorMatter, K
dc.contributor.authorFujita, Y
dc.date.accessioned2018-08-03T11:03:16Z
dc.date.issued2014-08
dc.identifier.citationJournal of cell science, 2014, 127 (Pt 16), pp. 3425 - 3433
dc.identifier.issn0021-9533
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2256
dc.identifier.eissn1477-9137
dc.identifier.doi10.1242/jcs.149674
dc.description.abstractAt the early stages of carcinogenesis, transformation occurs in single cells within tissues. In an epithelial monolayer, such mutated cells are recognized by their normal neighbors and are often apically extruded. The apical extrusion requires cytoskeletal reorganization and changes in cell shape, but the molecular switches involved in the regulation of these processes are poorly understood. Here, using stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative mass spectrometry, we have identified proteins that are modulated in transformed cells upon their interaction with normal cells. Phosphorylation of VASP at serine 239 is specifically upregulated in Ras(V12)-transformed cells when they are surrounded by normal cells. VASP phosphorylation is required for the cell shape changes and apical extrusion of Ras-transformed cells. Furthermore, PKA is activated in Ras-transformed cells that are surrounded by normal cells, leading to VASP phosphorylation. These results indicate that the PKA-VASP pathway is a crucial regulator of tumor cell extrusion from the epithelium, and they shed light on the events occurring at the early stage of carcinogenesis.
dc.formatPrint-Electronic
dc.format.extent3425 - 3433
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved
dc.subjectEpithelium
dc.subjectCell Line, Transformed
dc.subjectEpithelial Cells
dc.subjectHumans
dc.subjectCell Transformation, Neoplastic
dc.subjectMicrofilament Proteins
dc.subjectCyclic AMP-Dependent Protein Kinases
dc.subjectCell Adhesion Molecules
dc.subjectPhosphoproteins
dc.subjectPhosphorylation
dc.subjectProto-Oncogene Proteins p21(ras)
dc.titlePKA-regulated VASP phosphorylation promotes extrusion of transformed cells from the epithelium.
dc.typeJournal Article
rioxxterms.versionofrecord10.1242/jcs.149674
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2014-08
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfJournal of cell science
pubs.issuePt 16
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Cell Communication
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Cell Communication
pubs.publication-statusPublished
pubs.volume127
pubs.embargo.termsNot known
icr.researchteamCell Communicationen_US
dc.contributor.icrauthorJorgensen, Clausen
dc.contributor.icrauthorSinclair, Johnen


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