Involvement of orphan nuclear receptor COUP-TFII in cadherin-6 and cadherin-11 regulation: Implications in development and cancer

Changes in cadherin expression are instrumental both in embryonic development and disease, underlining the importance of understanding how cadherin expression is controlled. Kidney development is characterized by a mesenchymal-epithelial transition underlain by a cadherin-11 to cadherin-6 switch, the regulation mechanisms of which are presently unexplained. Using transfection and RNA-interference we demonstrate that COUP-TFII (NR2F2) induces down-regulation of cadherin-6 and up-regulation of cadherin-11 in cultured cell lines. Double immunolabeling of mouse embryos provides indirect evidence that COUP-TFII negatively controls the cadherin-11 to cadherin-6 switch underlying the kidney developmental mesenchymal-epithelial transition. Furthermore, we found high expression of COUP-TFII in some gastric and oesophageal adenocarcinomas, correlating with abnormal cadherin-11 expression and suggesting reactivation of embryonic pathways linked to COUP-TFII in these tumors. Altogether, our data shed new light upon the role of COUP-TFII in development and in cancer.