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

• COUP-TFII (NR2F2) regulates cadherin-6 and cadherin-11 expression in cultured cells.
• COUP-TFII (NR2F2) triggers a cadherin-6 to cadherin-11 switch in TPC1 cells.
• COUP-TFII expression matches the cadherin-11 to -6 switch on kidney development.
• COUP-TFII correlates with undue cadherin-11 expression in gastric/esophageal tumors.

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.