Activation of snail and EMT-like signaling via the IKKαβ/NF-κB pathway in Apicidin-resistant HA22T hepatocellular carcinoma cells.

Abstract

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.

• Authors: 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
• Journal: The Chinese journal of physiology (Chin J Physiol) Vol. 56 Issue 6 Pg. 326-33 (Dec 31 2013) ISSN: 0304-4920 [Print] India
• PMID: 24495179 (Publication Type: Journal Article)

Chemical References

• Histone Deacetylase Inhibitors
• NF-kappa B
• Peptides, Cyclic
• Snail Family Transcription Factors
• Transcription Factors
• apicidin
• Glycogen Synthase Kinase 3 beta
• I-kappa B Kinase
• Glycogen Synthase Kinase 3

Topics

• Carcinoma, Hepatocellular (pathology)
• Cell Line, Tumor
• Drug Resistance, Neoplasm
• Epithelial-Mesenchymal Transition
• Glycogen Synthase Kinase 3 (physiology)
• Glycogen Synthase Kinase 3 beta
• Histone Deacetylase Inhibitors (pharmacology)
• Humans
• I-kappa B Kinase (physiology)
• Liver Neoplasms (pathology)
• NF-kappa B (physiology)
• Peptides, Cyclic (pharmacology)
• Signal Transduction (physiology)
• Snail Family Transcription Factors
• Transcription Factors (physiology)