RRC ID 49276
Author Katsura A, Tamura Y, Hokari S, Harada M, Morikawa M, Sakurai T, Takahashi K, Mizutani A, Nishida J, Yokoyama Y, Morishita Y, Murakami T, Ehata S, Miyazono K, Koinuma D.
Title ZEB1-regulated inflammatory phenotype in breast cancer cells.
Journal Mol Oncol
Abstract Zinc finger E-box binding protein 1 (ZEB1) and ZEB2 induce epithelial-mesenchymal transition (EMT) and enhance cancer progression. However, the global view of transcriptional regulation by ZEB1 and ZEB2 is yet to be elucidated. Here, we identified a ZEB1-regulated inflammatory phenotype in breast cancer cells using chromatin immunoprecipitation sequencing and RNA sequencing, followed by gene set enrichment analysis (GSEA) of ZEB1-bound genes. Knockdown of ZEB1 and/or ZEB2 resulted in the downregulation of genes encoding inflammatory cytokines related to poor prognosis in patients with cancer, including IL6 and IL8, therefore suggesting that ZEB1 and ZEB2 have similar functions in terms of the regulation of production of inflammatory cytokines. Antibody array and ELISA experiments confirmed that ZEB1 controlled the production of the IL-6 and IL-8 proteins. The secretory proteins regulated by ZEB1 enhanced breast cancer cell proliferation and tumor growth. ZEB1 expression in breast cancer cells also affected the growth of fibroblasts in cell culture, and the accumulation of myeloid-derived suppressor cells in tumors in vivo. These findings provide insight into the role of ZEB1 in the progression of cancer, mediated by inflammatory cytokines, along with the initiation of EMT.
Volume 11(9)
Pages 1241-1262
Published 2017-9-1
DOI 10.1002/1878-0261.12098
PMID 28618162
PMC PMC5579340
MeSH Animals Base Sequence Biomarkers, Tumor / metabolism Cell Line, Tumor Cell Proliferation / drug effects Chemokines / metabolism Culture Media, Conditioned / pharmacology DNA, Neoplasm / metabolism Female Fibroblasts / drug effects Fibroblasts / metabolism Fibroblasts / pathology Gene Expression Regulation, Neoplastic Humans Inflammatory Breast Neoplasms / genetics Inflammatory Breast Neoplasms / metabolism Inflammatory Breast Neoplasms / pathology Mice, Inbred BALB C Mice, Nude Myeloid Cells / drug effects Myeloid Cells / metabolism Paracrine Communication / drug effects Phenotype Signal Transduction / drug effects Transforming Growth Factor beta / pharmacology Zinc Finger E-box Binding Homeobox 2 / metabolism Zinc Finger E-box-Binding Homeobox 1 / genetics Zinc Finger E-box-Binding Homeobox 1 / metabolism*
IF 6.574
Times Cited 35
DNA material CS-CDF-CG-PRE (RDB04379) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394).