Open Access

Adrenomedullin promotes intrahepatic cholangiocellular carcinoma metastasis and invasion by inducing epithelial-mesenchymal transition

  • Authors:
    • Chuang Zhou
    • Yan Zheng
    • Lin Li
    • Wenlong Zhai
    • Renfeng Li
    • Zhiwen Liang
    • Longshuan Zhao
  • View Affiliations

  • Published online on: June 5, 2015     https://doi.org/10.3892/or.2015.4034
  • Pages: 610-616
  • Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Intrahepatic cholangiocellular carcinoma (ICC) is the second most common type of primary liver cancer. However, its etiology and molecular pathogenesis remain largely unknown. The present study aimed to investigate the association between adrenomedullin (ADM) and epithelial-mesenchymal transition (EMT) in ICC and to elucidate the underlying signaling pathway. We evaluated the clinical significance of ADM in 133 ICC patients using tissue microarray analysis of ICC tissues. We also investigated the mechanisms of ADM in ICC EMT-mediated metastasis in cholangiocarcinoma cell lines in vitro. The results revealed that ADM was upregulated in human ICC tissues (73/133) compared with that in healthy controls. ADM expression was positively correlated with shorter overall survival (P<0.01). The characteristics of EMT were induced in vitro by adenoviral transduction of ADM into HuCCT1 cells, resulting in the downregulation of E-cadherin and ZO-1, and the concomitant upregulation of N-cadherin and vimentin. Knockdown of ADM by short hairpin RNA in HUH28 cells expressing high levels of ADM was associated with the reversal of EMT. Functional studies revealed that ADM regulated the activation of ZEB1, which subsequently mediated EMT. The results of the present study suggest that ADM plays an important role in ICC metastasis, and that ADM signaling of EMT may represent a valuable therapeutic target in cancer patients.
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August-2015
Volume 34 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Zhou C, Zheng Y, Li L, Zhai W, Li R, Liang Z and Zhao L: Adrenomedullin promotes intrahepatic cholangiocellular carcinoma metastasis and invasion by inducing epithelial-mesenchymal transition. Oncol Rep 34: 610-616, 2015.
APA
Zhou, C., Zheng, Y., Li, L., Zhai, W., Li, R., Liang, Z., & Zhao, L. (2015). Adrenomedullin promotes intrahepatic cholangiocellular carcinoma metastasis and invasion by inducing epithelial-mesenchymal transition. Oncology Reports, 34, 610-616. https://doi.org/10.3892/or.2015.4034
MLA
Zhou, C., Zheng, Y., Li, L., Zhai, W., Li, R., Liang, Z., Zhao, L."Adrenomedullin promotes intrahepatic cholangiocellular carcinoma metastasis and invasion by inducing epithelial-mesenchymal transition". Oncology Reports 34.2 (2015): 610-616.
Chicago
Zhou, C., Zheng, Y., Li, L., Zhai, W., Li, R., Liang, Z., Zhao, L."Adrenomedullin promotes intrahepatic cholangiocellular carcinoma metastasis and invasion by inducing epithelial-mesenchymal transition". Oncology Reports 34, no. 2 (2015): 610-616. https://doi.org/10.3892/or.2015.4034