Inhibition of BRD4 suppresses the malignancy of breast cancer cells via regulation of Snail.

ABSTRACT: The mechanistic action of bromodomain-containing protein 4 (BRD4) in cancer motility, including epithelial-mesenchymal transition (EMT), remains largely undefined. We found that targeted inhibition of BRD4 reduces migration, invasion, in vivo growth of patient-derived xenograft (PDX), and lung colonization of breast cancer (BC) cells. Inhibition of BRD4 rapidly decreases the expression of Snail, a powerful EMT transcription factor (EMT-TF), via diminishing its protein stability and transcription. Protein kinase D1 (PRKD1) is responsible for BRD4-regulated Snail protein stability by triggering phosphorylation at Ser11 of Snail and then inducing proteasome-mediated degradation. BRD4 inhibition also suppresses the expression of Gli1, a key transductor of Hedgehog (Hh) required to activate the

SUBMITTER: Lu L 

PROVIDER: S-EPMC7205888 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature