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Tumor necrosis factor-α (TNF-α) stimulates the epithelial–mesenchymal transition regulator Snail in cholangiocarcinoma

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Abstract

Epithelial–mesenchymal transition (EMT) is a series of events during which epithelial cells lose many of their epithelial characteristics and take on properties that are typical of mesenchymal cells that lack cell–cell adhesion properties. EMT may be activated by various types of growth factors or inflammatory cytokines. In many types of epithelial cancers, the EMT-derived tumor cells are susceptible to metastasis. During tumor progression, epithelial cells acquire a gene expression pattern closely resembling that of mesenchymal cells. This study aimed to investigate the expression of the EMT-associated transcription factor Snail and an adhesion molecule E-cadherin in cholangiocarcinoma (CCA) tissues. The effect of TNF-α on EMT activation in CCA cells was also demonstrated. The qRT-PCR analysis revealed that Snail expression significantly increased in CCA (P = 0.01) and was correlated with tumor metastasis (P = 0.02). The expression of Snail was inversely associated with E-cadherin (P = 0.004). The stimulation of TNF-α enhances migration behavior and showed significantly induced expression of Snail in CCA cell lines, whereas expression of E-cadherin and CK-19 (the epithelial marker) was reduced. Immunofluorescence analysis revealed that TNF-α-treated CCA cell lines increased nuclear translocation of Snail, whereas E-cadherin was dramatically decreased. Our findings suggest that the changes in the expression of Snail or E-cadherin might regulate EMT development in CCA resulting in promoting tumor progression. Overexpression of Snail could be used as a prognostic marker for monitoring the treatment efficiency of CCA patients.

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Acknowledgments

This work was supported by the Higher Education Research Promotion and National Research University Project of Thailand, Office of the Higher Education Commission, through the Health Cluster (SHeP-GMS), Khon Kaen University, Khon Kaen University Research Fund (Grant No. 541901). We wish to acknowledge the support of the Khon Kaen University Publication Clinic, Research and Technology Transfer Affairs, Khon Kaen University, for their assistance.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand

    Anchalee Techasen, Nisana Namwat, Watcharin Loilome, Pornpan Bungkanjana & Puangrat Yongvanit

  2. Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand

    Narong Khuntikeo

  3. Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand

    Anucha Puapairoj

  4. Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand

    Anchalee Techasen, Nisana Namwat, Watcharin Loilome, Pornpan Bungkanjana, Narong Khuntikeo, Anucha Puapairoj, Patcharee Jearanaikoon & Puangrat Yongvanit

  5. Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand

    Anchalee Techasen & Patcharee Jearanaikoon

  6. Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, Tokyo, Japan

    Hideyuki Saya

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  1. Anchalee Techasen
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Correspondence to Puangrat Yongvanit.

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Techasen, A., Namwat, N., Loilome, W. et al. Tumor necrosis factor-α (TNF-α) stimulates the epithelial–mesenchymal transition regulator Snail in cholangiocarcinoma. Med Oncol 29, 3083–3091 (2012). https://doi.org/10.1007/s12032-012-0305-x

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  • DOI: https://doi.org/10.1007/s12032-012-0305-x

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