Signal Transducing Adaptor Protein-2 Represses Epithelial-Mesenchymal Transition by Downregulating SMAD-Mediated ZEB1 Expression.

Abstract

Epithelial-mesenchymal transition (EMT) is crucial for initiation of cancer metastasis. EMT-induced epithelial cancer cells gain stemness characteristics, which enhance cancer malignancy and chemoresistance. Therefore, it is important to clarify the function of EMT-related genes for development of therapeutics for cancer metastasis. Here, we showed that Signal-transducing adaptor protein-2 (STAP-2) inhibits EMT in cancer cells through repressing SMAD-mediated ZEB1 expression, which is a master transcription factor of EMT. STAP-2 inhibits the interaction between SMAD3 and SMAD4, resulting in the downregulation of SMAD2/3/4 complex formation and TGF-β signal-induced gene expression. STAP-2 expression was repressed by SMAD2/3-mediated TGF-β signals and activated by OVOL1, which is one of the EMT repressor transcription factors. Our study showed that STAP-2 is a novel EMT repressor gene which represses ZEB1 expression and motility of cancer cells.