The role of ZEB1 in the inflammation-induced promotion of EMT in HNSCC

Abstract

Objectives To determine the role of ZEB1 in the inflammation-induced promotion of the epithelial-mesenchymal transition (EMT) in head and neck squamous cell carcinoma (HNSCC). Study Design A molecular biology study. Real-time quantitative reverse-transcriptase polymerase chain reaction (RT-PCR), Western blot analysis, and immunohistochemical staining of human HNSCC tissue sections were used to determine how inflammation affects the transcriptional repressor, ZEB1. Setting An academic hospital laboratory. Subjects and Methods Relative ZEB1 RNA levels were determined by RT-PCR, and protein expression was evaluated in situ by immunohistochemical staining of human HNSCC tissue sections. Results IL-1β-treated HNSCC cell lines demonstrated a significant decrease in E-cadherin mRNA and an increase in the mRNA expression of the transcriptional repressor ZEB1. IL-1β exposure led to enhanced ZEB1 binding at the chromatin level, as determined by chromatin immunoprecipitation assays (ChIP). An inverse relationship between ZEB1 and E-cadherin was demonstrated in situ by immunohistochemical staining of human HNSCC tissue sections. Conclusions Our recent investigations indicate that inflammatory mediators are potent regulators of EMT in HNSCC. This is the first report indicating the role of ZEB1 in the inflammation-induced promotion of EMT in HNSCC. This newly defined pathway for transcriptional regulation of E-cadherin in HNSCC has important implications for targeted chemoprevention and therapy.