Discoidin domain receptor 1 is a novel transcriptional target of ZEB1 in breast epithelial cells undergoing H-Ras-induced epithelial to mesenchymal transition.

ABSTRACT: The epithelial-to-mesenchymal transition (EMT) process allows carcinoma cells to dissociate from the primary tumor thereby facilitating tumor cell invasion and metastasis. Ras-dependent hyperactive signaling is commonly associated with tumorigenesis, invasion, EMT, and metastasis. However, the downstream effectors by which Ras regulates EMT remain ill defined. In this study, we show that the H-Ras pathway leads to mesenchymal-like phenotypic changes in human breast epithelial cells by controlling the ZEB1/microRNA-200c axis. Moreover, H-Ras suppresses the expression of the discoidin domain receptor 1 (DDR1), a collagen receptor tyrosine kinase, via ZEB1, thus identifying ZEB1 as a novel transcriptional repressor of DDR1. Mutation studies on the putative promoter of the DDR1 gene revealed t

SUBMITTER: Koh M 

PROVIDER: S-EPMC5033064 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature