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dc.date.accessioned2016-02-17T10:19:56Z
dc.date.available2016-02-17T10:19:56Z
dc.date.created2015-06-22T13:25:49Z
dc.date.issued2015
dc.identifier.citationLund, Kaja Dembinski, Jennifer Lynn Solberg, Nina Urbanucci, Alfonso Mills, Ian Geoffrey Krauss, Stefan . Slug-dependent upregulation of L1CAM is responsible for the increased invasion potential of pancreatic cancer cells following long-term 5-FU treatment. PLoS ONE. 2015, 10(4)
dc.identifier.urihttp://hdl.handle.net/10852/49186
dc.description.abstractBackground Pancreatic adenocarcinoma is a lethal disease with 5-year survival of less than 5%. 5-fluorouracil (5-FU) is a principal first-line therapy, but treatment only extends survival modestly and is seldom curative. Drug resistance and disease recurrence is typical and there is a pressing need to overcome this. To investigate acquired 5-FU resistance in pancreatic adenocarcinoma, we established chemoresistant monoclonal cell lines from the Panc 03.27 cell line by long-term exposure to increasing doses of 5-FU. Results 5-FU-resistant cell lines exhibited increased expression of markers associated with multidrug resistance explaining their reduced sensitivity to 5-FU. In addition, 5-FU-resistant cell lines showed alterations typical for an epithelial-to-mesenchymal transition (EMT), including upregulation of mesenchymal markers and increased invasiveness. Microarray analysis revealed the L1CAM pathway as one of the most upregulated pathways in the chemoresistant clones, and a significant upregulation of L1CAM was seen on the RNA and protein level. In pancreatic cancer, expression of L1CAM is associated with a chemoresistant and migratory phenotype. Using esiRNA targeting L1CAM, or by blocking the extracellular part of L1CAM with antibodies, we show that the increased invasiveness observed in the chemoresistant cells functionally depends on L1CAM. Using esiRNA targeting β-catenin and/or Slug, we demonstrate that in the chemoresistant cell lines, L1CAM expression depends on Slug rather than β-catenin. Conclusion Our findings establish Slug-induced L1CAM expression as a mediator of a chemoresistant and migratory phenotype in pancreatic adenocarcinoma cells.en_US
dc.languageEN
dc.language.isoenen_US
dc.publisherPublic Library of Science (PLoS)
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleSlug-dependent upregulation of L1CAM is responsible for the increased invasion potential of pancreatic cancer cells following long-term 5-FU treatmenten_US
dc.typeJournal articleen_US
dc.creator.authorLund, Kaja
dc.creator.authorDembinski, Jennifer Lynn
dc.creator.authorSolberg, Nina
dc.creator.authorUrbanucci, Alfonso
dc.creator.authorMills, Ian Geoffrey
dc.creator.authorKrauss, Stefan
cristin.unitcode185,29,22,0
cristin.unitnameCentre for Molecular Medicine Norway - Nordic EMBL Partnership
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.cristin1249862
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=PLoS ONE&rft.volume=10&rft.spage=&rft.date=2015
dc.identifier.jtitlePLoS ONE
dc.identifier.volume10
dc.identifier.issue4
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0123684
dc.identifier.urnURN:NBN:no-52961
dc.type.documentTidsskriftartikkelen_US
dc.type.peerreviewedPeer reviewed
dc.source.issn1932-6203
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/49186/1/Lund_2015_Slu.pdf
dc.type.versionPublishedVersion
cristin.articleide0123684


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