ZEB1-regulated inflammatory phenotype in breast cancer cells.
ZEB1-regulated inflammatory phenotype in breast cancer cells.
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DOI：
10.1002/1878-0261.12098
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发表时间：
2017-09
影响因子：
6.6
通讯作者：
Koinuma D
中科院分区：
文献类型：
--
作者：
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
锌指E - box结合蛋白1 （ZEB1）和ZEB2诱导上皮-间质转化（EMT）并促进癌症进展。然而，ZEB1和ZEB2转录调控的全局观点尚未阐明。在这里，我们使用染色质免疫沉淀测序和RNA测序，然后对ZEB1结合基因进行基因集富集分析（GSEA），在乳腺癌细胞中发现了ZEB1调节的炎症表型。敲低ZEB1和/或ZEB2导致癌症患者预后不良相关炎症因子编码基因IL6和IL8下调，提示ZEB1和ZEB2在调节炎症因子产生方面功能相似。抗体阵列和ELISA实验证实，ZEB1控制IL - 6和IL - 8蛋白的产生。ZEB1调节的分泌蛋白促进乳腺癌细胞增殖和肿瘤生长。ZEB1在乳腺癌细胞中的表达也影响了细胞培养中成纤维细胞的生长，以及肿瘤中髓源性抑制细胞的积累。这些发现提供了ZEB1在炎症细胞因子介导的癌症进展中的作用，以及EMT的开始。
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.
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影响因子：
11.2
作者：
Hartman ZC;Poage GM;den Hollander P;Tsimelzon A;Hill J;Panupinthu N;Zhang Y;Mazumdar A;Hilsenbeck SG;Mills GB;Brown PH
通讯作者：
Brown PH
影响因子：
64.5
作者：
Acharyya S;Oskarsson T;Vanharanta S;Malladi S;Kim J;Morris PG;Manova-Todorova K;Leversha M;Hogg N;Seshan VE;Norton L;Brogi E;Massagué J
通讯作者：
Massagué J
影响因子：
64.8
作者：
Fischer KR;Durrans A;Lee S;Sheng J;Li F;Wong ST;Choi H;El Rayes T;Ryu S;Troeger J;Schwabe RF;Vahdat LT;Altorki NK;Mittal V;Gao D
通讯作者：
Gao D
影响因子：
3.3
作者：
Gregory PA;Bracken CP;Smith E;Bert AG;Wright JA;Roslan S;Morris M;Wyatt L;Farshid G;Lim YY;Lindeman GJ;Shannon MF;Drew PA;Khew-Goodall Y;Goodall GJ
通讯作者：
Goodall GJ
影响因子：
15.9
作者：
Gao, Sizhi Paul;Mark, Kevin G.;Bromberg, Jacqueline F.
通讯作者：
Bromberg, Jacqueline F.