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International Journal of Oncology
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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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Article

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
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, Chonbuk National University, Medical School, Research Institute of Clinical Medicine of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju 561-756, Republic of Korea, Department of Internal Medicine, Chonbuk National University, Medical School, Research Institute of Clinical Medicine of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju 561-756, Republic of Korea
  • Pages: 691-698
    |
    Published online on: May 28, 2014
       https://doi.org/10.3892/ijo.2014.2472
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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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1 

Litvinov SV, Balzar M, Winter MJ, et al: Epithelial cell adhesion molecule (Ep-CAM) modulates cell-cell interactions mediated by classic cadherins. J Cell Biol. 139:1337–1348. 1997. View Article : Google Scholar : PubMed/NCBI

2 

Baeuerle PA and Gires O: EpCAM (CD326) finding its role in cancer. Br J Cancer. 96:417–423. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Went PT, Lugli A, Meier S, et al: Frequent EpCam protein expression in human carcinomas. Hum Pathol. 35:122–128. 2004. View Article : Google Scholar : PubMed/NCBI

4 

Munz M, Baeuerle PA and Gires O: The emerging role of EpCAM in cancer and stem cell signaling. Cancer Res. 69:5627–5629. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Patriarca C, Macchi RM, Marschner AK and Mellstedt H: Epithelial cell adhesion molecule expression (CD326) in cancer: a short review. Cancer Treat Rev. 38:68–75. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Schmidt M, Scheulen ME, Dittrich C, et al: An open-label, randomized phase II study of adecatumumab, a fully human anti-EpCAM antibody, as monotherapy in patients with metastatic breast cancer. Ann Oncol. 21:275–282. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Niedzwiecki D, Bertagnolli MM, Warren RS, et al: Documenting the natural history of patients with resected stage II adenocarcinoma of the colon after random assignment to adjuvant treatment with edrecolomab or observation: results from CALGB 9581. J Clin Oncol. 29:3146–3152. 2011. View Article : Google Scholar

8 

Maetzel D, Denzel S, Mack B, et al: Nuclear signalling by tumour-associated antigen EpCAM. Nat Cell Biol. 11:162–171. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Ralhan R, He HC, So AK, et al: Nuclear and cytoplasmic accumulation of Ep-ICD is frequently detected in human epithelial cancers. PLoS One. 5:e141302010. View Article : Google Scholar : PubMed/NCBI

10 

Carpenter G and Red Brewer M: EpCAM: another surface-to-nucleus missile. Cancer Cell. 15:165–166. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Schmalhofer O, Brabletz S and Brabletz T: E-cadherin, beta-catenin, and ZEB1 in malignant progression of cancer. Cancer Metastasis Rev. 28:151–166. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Polette M, Mestdagt M, Bindels S, et al: Beta-catenin and ZO-1: shuttle molecules involved in tumor invasion-associated epithelial-mesenchymal transition processes. Cells Tissues Organs. 185:61–65. 2007. View Article : Google Scholar

13 

Vincan E and Barker N: The upstream components of the Wnt signalling pathway in the dynamic EMT and MET associated with colorectal cancer progression. Clin Exp Metastasis. 25:657–663. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Paul S and Dey A: Wnt signaling and cancer development: therapeutic implication. Neoplasma. 55:165–176. 2008.PubMed/NCBI

15 

Khan SA, Thomas HC, Davidson BR and Taylor-Robinson SD: Cholangiocarcinoma. Lancet. 366:1303–1314. 2005. View Article : Google Scholar : PubMed/NCBI

16 

Blechacz B and Gores GJ: Cholangiocarcinoma: advances in pathogenesis, diagnosis, and treatment. Hepatology. 48:308–321. 2008. View Article : Google Scholar : PubMed/NCBI

17 

van der Gaag NA, Kloek JJ, de Bakker JK, et al: Survival analysis and prognostic nomogram for patients undergoing resection of extrahepatic cholangiocarcinoma. Ann Oncol. 23:2642–2649. 2012.PubMed/NCBI

18 

Kim DG, Park SY, You KR, et al: Establishment and characterization of chromosomal aberrations in human cholangiocarcinoma cell lines by cross-species color banding. Genes Chromosomes Cancer. 30:48–56. 2001. View Article : Google Scholar : PubMed/NCBI

19 

Bae JS, Noh SJ, Jang KY, et al: Expression and role of epithelial cell adhesion molecule in dysplastic nodule and hepatocellular carcinoma. Int J Oncol. 41:2150–2158. 2012.PubMed/NCBI

20 

Kwon CY, Kim KR, Choi HN, et al: The role of serum response factor in hepatocellular carcinoma: Implications for disease progression. Int J Oncol. 37:837–844. 2010.PubMed/NCBI

21 

Litvinov SV, Velders MP, Bakker HA, Fleuren GJ and Warnaar SO: Ep-CAM: a human epithelial antigen is a homophilic cell-cell adhesion molecule. J Cell Biol. 125:437–446. 1994. View Article : Google Scholar : PubMed/NCBI

22 

van der Gun BT, Melchers LJ, Ruiters MH, de Leij LF, McLaughlin PM and Rots MG: EpCAM in carcinogenesis: the good, the bad or the ugly. Carcinogenesis. 31:1913–1921. 2010.PubMed/NCBI

23 

Trzpis M, McLaughlin PM, de Leij LM and Harmsen MC: Epithelial cell adhesion molecule: more than a carcinoma marker and adhesion molecule. Am J Pathol. 171:386–395. 2007. View Article : Google Scholar : PubMed/NCBI

24 

Ralhan R, Cao J, Lim T, Macmillan C, Freeman JL and Walfish PG: EpCAM nuclear localization identifies aggressive thyroid cancer and is a marker for poor prognosis. BMC Cancer. 10:3312010. View Article : Google Scholar : PubMed/NCBI

25 

Warneke VS, Behrens HM, Haag J, et al: Members of the EpCAM signalling pathway are expressed in gastric cancer tissue and are correlated with patient prognosis. Br J Cancer. 109:2217–2227. 2013. View Article : Google Scholar : PubMed/NCBI

26 

Fong D, Moser P, Kasal A, et al: Loss of membranous expression of the intracellular domain of EpCAM is a frequent event and predicts poor survival in patients with pancreatic cancer. Histopathology. 64:683–692. 2014. View Article : Google Scholar : PubMed/NCBI

27 

Lin CW, Liao MY, Lin WW, Wang YP, Lu TY and Wu HC: Epithelial cell adhesion molecule regulates tumor initiation and tumorigenesis via activating reprogramming factors and epithelial-mesenchymal transition gene expression in colon cancer. J Biol Chem. 287:39449–39459. 2012. View Article : Google Scholar

28 

Gosens MJ, van Kempen LC, van de Velde CJ, van Krieken JH and Nagtegaal ID: Loss of membranous Ep-CAM in budding colorectal carcinoma cells. Mod Pathol. 20:221–232. 2007. View Article : Google Scholar : PubMed/NCBI

29 

Kessenbrock K, Plaks V and Werb Z: Matrix metalloproteinases: regulators of the tumor microenvironment. Cell. 141:52–67. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Denzel S, Mack B, Eggert C, et al: MMP7 is a target of the tumour-associated antigen EpCAM. Int J Exp Pathol. 93:341–353. 2012. View Article : Google Scholar : PubMed/NCBI

31 

Litvinov SV, van Driel W, van Rhijn CM, et al: Expression of Ep-CAM in cervical squamous epithelia correlates with an increased proliferation and the disappearance of markers for terminal differentiation. Am J Pathol. 148:865–875. 1996.

32 

Chaves-Pérez A, Mack B, Maetzel D, et al: EpCAM regulates cell cycle progression via control of cyclin D1 expression. Oncogene. 32:641–650. 2013.

33 

Osta WA, Chen Y, Mikhitarian K, et al: EpCAM is overexpressed in breast cancer and is a potential target for breast cancer gene therapy. Cancer Res. 64:5818–5824. 2004. View Article : Google Scholar : PubMed/NCBI

34 

Yamashita T, Ji J, Budhu A, et al: EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features. Gastroenterology. 136:1012–1024. 2009. View Article : Google Scholar : PubMed/NCBI

35 

Münz M, Kieu C, Mack B, Schmitt B, Zeidler R and Gires O: The carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation. Oncogene. 23:5748–5758. 2004.PubMed/NCBI

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Copy and paste a formatted citation
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
Copy and paste a formatted citation
x
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
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