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Targeted disruption of Nemo‐like kinase inhibits tumor cell growth by simultaneous suppression of cyclin D1 and CDK2 in human hepatocellular carcinoma
Author(s) -
Jung Kwang Hwa,
Kim Jeong Kyu,
Noh Ji Heon,
Eun Jung Woo,
Bae Hyun Jin,
Xie Hong Jian,
Ahn Young Min,
Park Won Sang,
Lee Jung Young,
Nam Suk Woo
Publication year - 2010
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22579
Subject(s) - wnt signaling pathway , cancer research , cyclin dependent kinase 2 , hccs , cyclin d1 , cyclin e1 , cell cycle , carcinogenesis , cell growth , biology , cell , cancer , signal transduction , hepatocellular carcinoma , microbiology and biotechnology , genetics
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.