The role of nuclear EpICD in extrahepatic cholangiocarcinoma: Association with β-catenin

  • Authors:
    • Sarangerel Jachin
    • Jun Sang Bae
    • Jong Jin Sung
    • Ho Sung Park
    • Kyu Yun Jang
    • Myoung Ja Chung
    • Dae Gohn Kim
    • Woo Sung Moon
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  • Published online on: May 28, 2014     https://doi.org/10.3892/ijo.2014.2472
  • Pages: 691-698
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Abstract

After intramembranous proteolysis-mediated loss of the extracellular domain of the epithelial cell adhesion molecule (EpEx) and release of an intracellular domain (EpICD) into the cytoplasm, EpICD sequentially associates with FHL2 to form a nuclear complex with β-catenin and Lef-1. This association induces gene transcription involved in the activation of the oncogenic potential of epithelial cell adhesion molecule (EpCAM). We examined the localization and expression of EpEx, EpICD and β-catenin in surgical specimens of extrahepatic cholangiocarcinoma (ECC) from 79 patients and focused on the relationship between nuclear expression of EpICD and β-catenin. We also examined the role of EpICD by transfecting the EpICD cDNA in cholangiocarcinoma (CC) cell lines. There was a significant correlation between the nuclear expression of EpICD and β-catenin in ECC tissues. Frequent nuclear co-localization of EpICD and β-catenin was observed in cancer cells forming the invasive front. Nuclear expression of EpICD also significantly correlated with histologic grade of tumor. Overexpression of EpICD in the CC cells significantly increased the cell growth and proliferation. The overexpression of EpICD in the CC cells also increased the expression levels of the active form of β-catenin and EpCAM target genes, such as c-myc and cyclin D1. Furthermore, the overexpression of EpICD significantly enhanced the migration and invasiveness of CC cells. Conversely, the inhibition of EpCAM in EpCAM-overexpressing cells by siRNA significantly decreased cell proliferation, migration and invasion. These results indicate that the spatial localization of EpICD and its mutual interaction with β-catenin may be important in ECC progression and invasion.
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August-2014
Volume 45 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Jachin S, Bae JS, Sung JJ, Park HS, Jang KY, Chung MJ, Kim DG and Moon WS: The role of nuclear EpICD in extrahepatic cholangiocarcinoma: Association with β-catenin. Int J Oncol 45: 691-698, 2014
APA
Jachin, S., Bae, J.S., Sung, J.J., Park, H.S., Jang, K.Y., Chung, M.J. ... Moon, W.S. (2014). The role of nuclear EpICD in extrahepatic cholangiocarcinoma: Association with β-catenin. International Journal of Oncology, 45, 691-698. https://doi.org/10.3892/ijo.2014.2472
MLA
Jachin, S., Bae, J. S., Sung, J. J., Park, H. S., Jang, K. Y., Chung, M. J., Kim, D. G., Moon, W. S."The role of nuclear EpICD in extrahepatic cholangiocarcinoma: Association with β-catenin". International Journal of Oncology 45.2 (2014): 691-698.
Chicago
Jachin, S., Bae, J. S., Sung, J. J., Park, H. S., Jang, K. Y., Chung, M. J., Kim, D. G., Moon, W. S."The role of nuclear EpICD in extrahepatic cholangiocarcinoma: Association with β-catenin". International Journal of Oncology 45, no. 2 (2014): 691-698. https://doi.org/10.3892/ijo.2014.2472