Open AccessZEB 1‐regulated inflammatory phenotype in breast cancer cells
Author(s) -
Katsura Akihiro,
Tamura Yusuke,
Hokari Satoshi,
Harada Mayumi,
Morikawa Masato,
Sakurai Tsubasa,
Takahashi Kei,
Mizutani Anna,
Nishida Jun,
Yokoyama Yuichiro,
Morishita Yasuyuki,
Murakami Takashi,
Ehata Shogo,
Miyazono Kohei,
Koinuma Daizo
Publication year - 2017
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12098
Subject(s) - biology , cancer research , chromatin immunoprecipitation , carcinogenesis , downregulation and upregulation , breast cancer , gene knockdown , cancer , microbiology and biotechnology , gene expression , gene , promoter , genetics
Zinc finger E‐box binding protein 1 ( ZEB 1) and ZEB 2 induce epithelial‐mesenchymal transition ( EMT ) and enhance cancer progression. However, the global view of transcriptional regulation by ZEB 1 and ZEB 2 is yet to be elucidated. Here, we identified a ZEB 1‐regulated inflammatory phenotype in breast cancer cells using chromatin immunoprecipitation sequencing and RNA sequencing, followed by gene set enrichment analysis ( GSEA ) of ZEB 1‐bound genes. Knockdown of ZEB 1 and/or ZEB 2 resulted in the downregulation of genes encoding inflammatory cytokines related to poor prognosis in patients with cancer, including IL 6 and IL 8 , therefore suggesting that ZEB 1 and ZEB 2 have similar functions in terms of the regulation of production of inflammatory cytokines. Antibody array and ELISA experiments confirmed that ZEB 1 controlled the production of the IL ‐6 and IL ‐8 proteins. The secretory proteins regulated by ZEB 1 enhanced breast cancer cell proliferation and tumor growth. ZEB 1 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 ZEB 1 in the progression of cancer, mediated by inflammatory cytokines, along with the initiation of EMT .