Bioscience, Biotechnology, and Biochemistry
Online ISSN : 1347-6947
Print ISSN : 0916-8451
Biochemistry & Molecular Biology Regular Papers
Apicidin-Resistant HA22T Hepatocellular Carcinoma Cells strongly activated the Wnt/β-Catenin Signaling Pathway and MMP-2 Expression via the IGF-IR/PI3K/Akt Signaling Pathway Enhancing Cell Metastatic Effect
Cheng-Hong HSIEHLi-Hao CHENGHsi-Hsien HSUTsung-Jung HOChuan-Chou TUYueh-Min LINMing-Cheng CHENFuu-Jen TSAIYou-Liang HSIEHChih-Yang HUANG
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2013 Volume 77 Issue 12 Pages 2397-2404

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Abstract

The IGF-IR/PI3K/Akt signaling pathway inhibited GSK3-β activity by phosphorylation and this promoted β-catenin nuclear localization. Our previous study indicated that β-catenin mRNA level was significantly higher in tumor areas than in non-tumor ones, especially in late pathologic stage tumors. However, β-catenin inhibition resulted in significantly suppressed migration and invasion ability of HA22T cells. Thus, Wnt/β-catenin pathway over-activation might be involved in metastatic enhancement of apicidin-resistant HA22T cell metastasis. Apicidin-resistant (AR) HA22T cells showed higher β-catenin nuclear accumulation and significantly decreased GSK-3-β protein level, in relation to parental cells. Results also indicated that AR cells increased abundantly in Tbx3, a downstream target of Wnt/β-catenin that it is implicated in liver cancer. AR cells also inhibited the MEK/ERK/PEA3 pathway which promoted MMP-2 activation. But, apicidin-resistant effect was totally reversed by LY294002 and AG1024. In conclusion, Apicidin-R HA22T cells activated the Wnt/β-catenin pathway and induced, MMP-2 expression via IGF-IR/PI3K/Akt signaling further enhancing cell the metastatic effects.

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© 2013 by Japan Society for Bioscience, Biotechnology, and Agrochemistry
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