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dc.contributor.authorAbdollahi, Pegah
dc.contributor.authorVandsemb, Esten Nymoen
dc.contributor.authorHjort, Magnus Aassved
dc.contributor.authorMisund, Kristine
dc.contributor.authorHolien, Toril
dc.contributor.authorSponaas, Anne-Marit
dc.contributor.authorRø, Torstein Baade
dc.contributor.authorSlørdahl, Tobias Schmidt
dc.contributor.authorBørset, Magne
dc.date.accessioned2017-08-16T06:44:42Z
dc.date.available2017-08-16T06:44:42Z
dc.date.created2017-01-15T20:12:04Z
dc.date.issued2016
dc.identifier.citationMolecular Cancer Research. 2016, 15 (1), 69-77.nb_NO
dc.identifier.issn1541-7786
dc.identifier.urihttp://hdl.handle.net/11250/2450824
dc.description.abstractPhosphatase of regenerating liver-3 (PTP4A3/PRL-3) is a dual-specificity phosphatase that is upregulated in various types of cancers and is related to poor prognosis and aggressive tumor behavior. The expression level of PRL-3 is elevated in response to several antiapoptotic cytokines, including IL6, in cancer cells from patients with multiple myeloma (MM) and can promote survival and migration. Here, it is demonstrated that PRL-3 activates Src kinase in the IL6-dependent MM cell line INA-6. Inhibition of PRL-3 by a small-molecule inhibitor of PRL-3 or by shRNA resulted in inactivation of Src. In addition to activation of Src, PRL-3 also activated the Src family kinase (SFK) members LYN and HCK in INA-6 cells. Forced expression of catalytically inactive mutant PRL-3 decreased the activation of these three SFK members while the total level of HCK and FYN remained elevated. Inhibitors of Src increased sensitivity of cells overexpressing PRL-3 to the PRL-3 inhibitor through joint downregulation of both PRL-3 and Mcl-1. In conclusion, PRL-3 protected MM cells against apoptosis by dysregulating both the total levels and the activation levels of specific SFK members that are important for IL6 signal transduction in MM cells. Eventually, this led to increased levels of Mcl-1.nb_NO
dc.language.isoengnb_NO
dc.publisherAmerican Association for Cancer Researchnb_NO
dc.titleSrc family kinases are regulated in multiple myeloma cells by phosphatase of regenerating liver-3nb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.description.versionacceptedVersionnb_NO
dc.source.pagenumber69-77nb_NO
dc.source.volume15nb_NO
dc.source.journalMolecular Cancer Researchnb_NO
dc.source.issue1nb_NO
dc.identifier.doi10.1158/1541-7786.MCR-16-0212
dc.identifier.cristin1427636
dc.description.localcode© 2016 American Association for Cancer Research. This is the authors' accepted and refereed manuscript to the article. Locked until October 3 2017 due to copyright restrictions.nb_NO
cristin.unitcode194,65,15,0
cristin.unitnameInstitutt for kreftforskning og molekylær medisin
cristin.ispublishedtrue
cristin.fulltextpostprint
cristin.qualitycode1


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