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

The Wnt/beta-catenin signaling pathway regulates various aspects of development and plays important role in human carcinogenesis. Nemo-like kinase (NLK), which is mediator of Wnt/beta-catenin signaling pathway, phosphorylates T-cell factor/lymphoid enhancer factor (TCF/LEF) factor and inhibits interaction of beta-catenin/TCF complex. Although, NLK is known to be a tumor suppressor in Wnt/beta-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.

Jung KH ，Kim JK ，Noh JH ，Eun JW ，Bae HJ ，Xie HJ ，Ahn YM ，Park WS ，Lee JY ，Nam SW ... -  《-》

Targeted disruption of S100P suppresses tumor cell growth by down-regulation of cyclin D1 and CDK2 in human hepatocellular carcinoma.

Kim JK ，Jung KH ，Noh JH ，Eun JW ，Bae HJ ，Xie HJ ，Ahn YM ，Ryu JC ，Park WS ，Lee JY ，Nam SW ... -  《-》

Coordinated expression of cyclin D1 and LEF-1/TCF transcription factor is restricted to a subset of hepatocellular carcinoma.

Schmitt-Graeff A ，Ertelt-Heitzmann V ，Allgaier HP ，Olschewski M ，Nitschke R ，Haxelmans S ，Koelble K ，Behrens J ，Blum HE ... -  《LIVER INTERNATIONAL》

Aberrant expression and function of TCF4 in the proliferation of hepatocellular carcinoma cell line BEL-7402.

Zhao DH ，Hong JJ ，Guo SY ，Yang RL ，Yuan J ，Wen CY ，Zhou KY ，Li CJ ... -  《CELL RESEARCH》

Notch1 signaling inhibits growth of human hepatocellular carcinoma through induction of cell cycle arrest and apoptosis.

Qi R ，An H ，Yu Y ，Zhang M ，Liu S ，Xu H ，Guo Z ，Cheng T ，Cao X ... -  《CANCER RESEARCH》