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Carcinogenesis. 2014 Aug;35(8):1855-62. doi: 10.1093/carcin/bgu109. Epub 2014 May 19.

Evidence for a role of E-cadherin in suppressing liver carcinogenesis in mice and men.

Author information

1
Institute for Biotechnology and Molecular Animal Breeding, The Gene Center.
2
Institute for Biotechnology and Molecular Animal Breeding, The Gene Center, Department of Internal Medicine II and.
3
Laboratory for Functional Genome Analysis, The Gene Center, University of Munich, 81377 Munich, Germany.
4
Department of Surgery, University of Magdeburg, Magdeburg, Germany.
5
Institute of Pathology, University of Heidelberg, Heidelberg, Germany.
6
Institute of Pathology, University of Munich, 80337 Munich, Germany and.
7
Department of Internal Medicine II and.
8
Department of Internal Medicine II and German Cancer Consortium (DKTK) and the German Cancer Research Center, Heidelberg, Germany fkolligs@med.uni-muenchen.de.

Abstract

The cell adhesion molecule E-cadherin has critical functions in development and carcinogenesis. Impaired expression of E-cadherin has been associated with disrupted tissue homeostasis, progression of cancer and a worse patient prognosis. So far, the role of E-cadherin in homeostasis and carcinogenesis of the liver is not well understood. By use of a mouse model with liver-specific deletion of E-cadherin and administration of the carcinogen diethylnitrosamine, we demonstrate that loss of E-cadherin expression in hepatocytes results in acceleration of the growth of hepatocellular carcinoma (HCC). In contrast, liver regeneration is not disturbed in mice lacking E-cadherin expression in hepatocytes. In human HCC, we observed four different expression patterns of E-cadherin. Notably, atypical cytosolic expression of E-cadherin was positively correlated with a poorer patient prognosis. The median overall survival of patients with HCC expressing E-cadherin on the membrane only was 221 weeks (95% confidence interval: 51-391) compared with 131 weeks in patients with cytosolic expression (95% confidence interval: 71-191 weeks; P < 0.05). In conclusion, we demonstrate that impaired expression of E-cadherin promotes hepatocellular carcinogenesis and is associated with a worse prognosis in humans.

PMID:
24840851
DOI:
10.1093/carcin/bgu109
[Indexed for MEDLINE]

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