Activation of Snail and EMT-Like Signaling via the IKKαβ/NF-κB Pathway in Apicidin-Resistant HA22T Hepatocellular Carcinoma Cells

Chuan-Chou Tu ； Li-Hao Cheng ； Hsi-Hsien Hsu ； Li-Mien Chen ； Yueh-Min Lin ； Ming-Cheng Chen ； Nien-Hung Lee ； Fuu-Jen Tsai ； Chih-Yang Huang ； Wen-Jun Wu

《The Chinese Journal of Physiology》 56卷6期 (2013/12) Pp. 326-333

https://doi.org/10.4077/CJP.2013.BAB158

並列摘要

The molecular and phenotypic associations between chemo- or radio-resistance and the acquisition of epithelial-mesenchymal transition (EMT)-like phenotype are tightly related in cancer cells. Wnt/β- catenin and NF-κB signaling pathways play crucial roles in EMT induction. Apicidin-resistant (Apicidin- R) HA22T cells are known to activate the Wnt/β-catenin signaling pathway and MMP-2 expression via the IGF-IR/PI3K/Akt signaling pathway to enhance metastatic effects of cancer cells. In this study, we further investigated if Apicidin-R HA22T cells actually underwent EMT. In Apicidin-R HA22T cells, E-cadherin protein level was reduced but Vimentin, Snail and Twist were significantly activated. Activation of p-IKKαβ and p-IκBα was also observed in Apicidin-R HA22T cells. Apicidin-R HA22T cells displayed even higher NF-κB nuclear accumulation. Snail was enhanced but GSK3-β was reduced. However, unphosphorylated GSK3-β protein level was totally reversed when the Snail-specific siRNA was applied in a knockdown experiment. Taken together, Apicidin-R HA22T cells could potentiate aggressive metastasis behavior due to up-regulation of Snail expression and promoted EMT effects via the IKKαβ/NF-κB pathway. In addition, Snail might decrease the GSK3-β level resulting in extraordinarily activation of Wnt/β-catenin signaling pathway.

並列關鍵字

apicidin ； EMT ； HA22T ； IKKαβ ； NF-κB ； Snail

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