Alternative promotion and suppression of metastasis by JNK2 governed by its phosphorylation

Abstract

Fos-related antigen 1 (Fra1) has been proposed as a gatekeeper of the mesenchymal-epithelial transition to epithelial-mesenchymal transition. Here, we showed that de-phosphorylated JNK2 increased the expression of Fra1 by promoting the expression of c-Jun and Jun-B. Conversely, phosphorylated JNK2 suppressed its expression via enhancing the ubiquitination of c-Jun and Jun-B. These data provided insights into the regulatory mechanism of JNK2 on the expression of Fra1. Our study thus demonstrated that the conversion of JNK2 from its phosphorylation to de-phosphorylation status promoted the switch of breast cancer cells from mesenchymal-epithelial transition to epithelial-mesenchymal transition.