Nuclear legumain activity in colorectal cancer.
Nuclear legumain activity in colorectal cancer.
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DOI：
10.1371/journal.pone.0052980
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Maelandsmo GM
中科院分区：
文献类型：
--
作者：
Haugen MH;Johansen HT;Pettersen SJ;Solberg R;Brix K;Flatmark K;Maelandsmo GM
半胱氨酸蛋白酶legumain参与多种生物学和病理学过程，并且已经发现该蛋白酶在许多实体瘤中过表达并与侵袭性和转移性表型相关。因此，豆荚蛋白已被提出作为某些癌症的预后标志物和潜在的治疗靶点。然而，关于豆荚蛋白如何通过调节其蛋白水解活性而沿着恶性进展的细节尚不清楚。在目前的工作中，legumain的表达在结直肠癌细胞系进行了检查。在HCT 116和SW 620细胞和相应的皮下异种移植物中观察到前豆荚形式和活性豆荚形式的量存在显着差异，并且沿着不同的细胞内分布模式。Legumain被认为主要位于内-溶酶体中并加工成其活性形式;然而，亚细胞分布在很大程度上仍未探索。通过分析亚细胞组分，除了典型的内-溶酶体驻留外，在两种细胞系的细胞核中发现了蛋白水解活性形式的豆荚蛋白。Legumain表达和活性的原位分析证实了培养细胞中的内-溶酶体和核定位，重要的是，还证实了来自结肠直肠癌患者的异种移植物和活检切片中的内-溶酶体和核定位。在HCT 116和SW 620细胞系中，发现核豆荚蛋白分别占总豆荚蛋白的约13%和17%。与先前对相关半胱氨酸蛋白酶的核变体的研究相似，豆荚蛋白被证明加工组蛋白H3.1。核定位豆荚蛋白的发现为豆荚蛋白在癌症中的生物学和功能开辟了一个全新的竞技场。
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.
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影响因子：
3.8
作者：
Briggs JJ;Haugen MH;Johansen HT;Riker AI;Abrahamson M;Fodstad Ø;Maelandsmo GM;Solberg R
通讯作者：
Solberg R
影响因子：
25.7
作者：
Andrade V;Guerra M;Jardim C;Melo F;Silva W;Ortega JM;Robert M;Nathanson MH;Leite F
通讯作者：
Leite F
影响因子：
8.4
作者：
Flatmark, K;Mælandsmo, GM;Fodstad, O
通讯作者：
Fodstad, O
DOI：
10.1073/pnas.0809824105
发表时间：
2009-01-13
影响因子：
11.1
作者：
Chan, Chi-Bun;Abe, Michiyo;Ye, Keqiang
通讯作者：
Ye, Keqiang
影响因子：
11.6
作者：
HARANISHIMURA, I;TAKEUCHI, Y;NISHIMURA, M
通讯作者：
NISHIMURA, M