Evidence for a role of E-cadherin in suppressing liver carcinogenesis in mice and men
Menée à l'aide de modèles murins et de données portant sur des patients atteints d'un carcinome hépatocellulaire, cette étude met en évidence des mécanismes par lesquels une perte d'expression de l'E-cadhérine favorise la croissance tumorale et montre qu'elle est associée à un pronostic défavorable
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 diethylnitrosamin, 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 (CI), 51–391) compared to 131 weeks in patients with cytosolic expression (95% CI, 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.
http://carcin.oxfordjournals.org/content/early/2014/05/19/carcin.bgu109.abstract 2014