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dc.contributor.authorHaugen, Mads Haugland
dc.contributor.authorJohansen, Harald Thidemann
dc.contributor.authorPettersen, Solveig
dc.contributor.authorSolberg, Rigmor
dc.contributor.authorBrix, Klaudia
dc.contributor.authorFlatmark, Kjersti
dc.contributor.authorMælandsmo, Gunhild
dc.date.accessioned2014-03-20T14:48:18Z
dc.date.available2014-03-20T14:48:18Z
dc.date.issued2013
dc.description.abstractThe cysteine protease legumain is involved in several biological and pathological processes, and the protease has been found over-expressed and associated with an invasive and metastatic phenotype in a number of solid tumors. Consequently, legumain has been proposed as a prognostic marker for certain cancers, and a potential therapeutic target. Nevertheless, details on how legumain advances malignant progression along with regulation of its proteolytic activity are unclear. In the present work, legumain expression was examined in colorectal cancer cell lines. Substantial differences in amounts of pro- and active legumain forms, along with distinct intracellular distribution patterns, were observed in HCT116 and SW620 cells and corresponding subcutaneous xenografts. Legumain is thought to be located and processed towards its active form primarily in the endo-lysosomes; however, the subcellular distribution remains largely unexplored. By analyzing subcellular fractions, a proteolytically active form of legumain was found in the nucleus of both cell lines, in addition to the canonical endo-lysosomal residency. In situ analyses of legumain expression and activity confirmed the endo-lysosomal and nuclear localizations in cultured cells and, importantly, also in sections from xenografts and biopsies from colorectal cancer patients. In the HCT116 and SW620 cell lines nuclear legumain was found to make up approximately 13% and 17% of the total legumain, respectively. In similarity with previous studies on nuclear variants of related cysteine proteases, legumain was shown to process histone H3.1. The discovery of nuclear localized legumain launches an entirely novel arena of legumain biology and functions in cancer.en
dc.identifier.citationPLoS ONE (2013), vol. 8(1): e52980en
dc.identifier.cristinIDFRIDAID 1001508
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0052980
dc.identifier.issn1932-6203
dc.identifier.urihttps://hdl.handle.net/10037/6005
dc.identifier.urnURN:NBN:no-uit_munin_5715
dc.language.isoengen
dc.publisherPublic Library of Science (PLoS)en
dc.rights.accessRightsopenAccess
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762en
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762en
dc.titleNuclear Legumain Activity in Colorectal Canceren
dc.typeJournal articleen
dc.typeTidsskriftartikkelen
dc.typePeer revieweden


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