Functional Hierarchy and Cooperation of EMT Master Transcription Factors in Breast Cancer Metastasis.

ABSTRACT: Several master transcription factors (TF) can activate the epithelial-to-mesenchymal transition (EMT). However, their individual and combinatorial contributions to EMT in breast cancer are not defined. We show that overexpression of EMT-TFs individually in epithelial cells upregulated endogenous SNAI2, ZEB1/2, TCF4, and TWIST1/2 as a result of positive feedback mediated in part by suppression of their negative regulator miRNAs miR200s/203/205. We identified TCF4 as a potential new target of miR200s. Expression of ZEB1/2 strongly correlated with the mesenchymal phenotype in breast cancer cells, with the CD24^-/CD44⁺ stemness profile, and with lower expression of core epithelial genes in human breast tumors. Knockdown of EMT-TFs identified the key role of ZEB1 and its fu

SUBMITTER: Addison JB 

PROVIDER: S-EPMC8137545 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature