Targeted disruption of Nemo-like kinase inhibits tumor cell growth by simultaneous suppression of cyclin D1 and CDK2 in human hepatocellular carcinoma

Authors

  • Kwang Hwa Jung,

    1. Department of Pathology, Microdissection Genomics Research Center, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea
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  • Jeong Kyu Kim,

    1. Department of Pathology, Microdissection Genomics Research Center, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea
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  • Ji Heon Noh,

    1. Department of Pathology, Microdissection Genomics Research Center, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea
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  • Jung Woo Eun,

    1. Department of Pathology, Microdissection Genomics Research Center, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea
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  • Hyun Jin Bae,

    1. Department of Pathology, Microdissection Genomics Research Center, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea
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  • Hong Jian Xie,

    1. Department of Pathology, Microdissection Genomics Research Center, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea
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  • Young Min Ahn,

    1. Department of Kidney System, College of Oriental Medicine, Kyung Hee University, Seoul, Korea
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  • Won Sang Park,

    1. Department of Pathology, Microdissection Genomics Research Center, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea
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  • Jung Young Lee,

    1. Department of Pathology, Microdissection Genomics Research Center, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea
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  • Suk Woo Nam

    Corresponding author
    1. Department of Pathology, Microdissection Genomics Research Center, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea
    • Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea.
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Abstract

The Wnt/β-catenin signaling pathway regulates various aspects of development and plays important role in human carcinogenesis. Nemo-like kinase (NLK), which is mediator of Wnt/β-catenin signaling pathway, phosphorylates T-cell factor/lymphoid enhancer factor (TCF/LEF) factor and inhibits interaction of β-catenin/TCF complex. Although, NLK is known to be a tumor suppressor in Wnt/β-catenin signaling pathway of colon cancer, the other events occurring downstream of NLK pathways in other types of cancer remain unclear. In the present study, we identified that expression of NLK was significantly up-regulated in the HCCs compared to corresponding normal tissues in five selected tissue samples. Immunohistochemical analysis showed significant over-expression of NLK in the HCCs. Targeted-disruption of NLK suppressed cell growth and arrested cell cycle transition. Suppression of NLK elicited anti-mitogenic properties of the Hep3B cells by simultaneous inhibition of cyclinD1 and CDK2. The results of this study suggest that NLK is aberrantly regulated in HCC, which might contribute to the mitogenic potential of tumor cells during the initiation and progression of hepatocellular carcinoma; this process appears to involve the induction of CDK2 and cyclin D1 and might provide a novel target for therapeutic intervention in patients with liver cancer. J. Cell. Biochem. 110: 687–696, 2010. © 2010 Wiley-Liss, Inc.

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