Nuclear Legumain Activity in Colorectal Cancer
Permanent lenke
https://hdl.handle.net/10037/6005Dato
2013Type
Journal articleTidsskriftartikkel
Peer reviewed
Forfatter
Haugen, Mads Haugland; Johansen, Harald Thidemann; Pettersen, Solveig; Solberg, Rigmor; Brix, Klaudia; Flatmark, Kjersti; Mælandsmo, GunhildSammendrag
The 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.
Forlag
Public Library of Science (PLoS)Sitering
PLoS ONE (2013), vol. 8(1): e52980Metadata
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