Dysfunction of the Reciprocal Feedback Loop between GATA3- and ZEB2-Nucleated Repression Programs Contributes to Breast Cancer Metastasis

“…Real-time quantitative reverse transcription PCR (qPCR) was performed essentially the same as previously described (48,49). The primers are provided in Supplemental Table 5.…”

Section: Acknowledgmentsmentioning

confidence: 99%

The FOXN3-NEAT1-SIN3A repressor complex promotes progression of hormonally responsive breast cancer

Zhang

Liu

et al. 2017

Journal of Clinical Investigation

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163

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“…Expanding and differential roles of ZEB1 and ZEB2 have been identified in various types of cancers in recent years (Chaffer et al ., 2013; Krebs et al ., 2017; Mejlvang et al ., 2007; Morel et al ., 2017; Si et al ., 2015; Spaderna et al ., 2008). ZEB1 is expressed primarily in nonepithelial cells, and a genome‐wide analysis of ZEB1‐binding regions performed in an adipogenesis model clearly shows its physiological importance (Gubelmann et al ., 2014).…”

Section: Discussionmentioning

confidence: 99%

ZEB1‐regulated inflammatory phenotype in breast cancer cells

et al. 2017

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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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“…Zinc-finger E-box-binding homeobox (ZEB) 1 and ZEB2 are transcription factors for marginal zone B cells, which induce the epithelial-mesenchymal transition and promote metastasis in different types of cancer (15,16). In H. pylori-positive gastric diffuse large B-cell lymphoma, the inhibition of ZEB1 by miR-200 leads to a less aggressive form of the disease (17).…”

Section: Clinical Manifestations and Epigenetic Mechanisms Of Gastricmentioning

confidence: 99%

Clinical manifestations and epigenetic mechanisms of gastric mucosa associated lymphoid tissue lymphoma and long‑term follow‑up following Helicobacterï¿½pylori eradication

Song

Jiang

et al. 2017

Exp Ther Med

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Abstract. The current study aimed to summarize the clinical manifestations and identify the epigenetic mechanisms of gastric mucosa associated lymphoid tissue (MALT) lymphoma, as well as evaluate the long-term effects of Helicobacter pylori (H. pylori) eradication. A total of 122 patients with marginal zone B-cell lymphoma of primary gastric MALT lymphoma were enrolled in the present study. The clinical manifestations of gastric MALT lymphoma, including symptoms, H. pylori state and endoscopic type, were summarized. The response to therapy was evaluated in patients that underwent H. pylori eradication. Survival analysis was estimated using the Kaplan-Meier method. The expression of microRNA-383 (miR-383) in tumor tissues and cell lines was determined using reverse transcription quantitative polymerase chain reaction. Furthermore, bioinformatic analyses, luciferase reporter assays. and western blot analysis identified zinc finger E-box binding homeobox 2 (ZEB2) as a direct target gene of miR-383. An MTT assay was used to examine the function of miR-383 and ZEB2 in MALT lymphoma. The clinical symptoms of patients with gastric MALT lymphoma were non-specific and included epigastric pain, abdominal discomfort and bleeding. The majority of endoscopic types were classified as ulcer, erosion and mucosa edema. The H. pylori infection rate was 79.5% (97/122) and a total of 47 patients underwent eradication therapy. Lymphoma remission was achieved in 93.6% (44/47) of patients and complete remission (CR) was achieved in 74.4% (35/47). The median follow-up time was 38 months (range, 10-132 months) and the median time taken to achieve CR was 4 months (range, 3-7 months). The estimated 3-year survival rate was 90.3% and the 5-year survival rate was 76.2%. Therefore, it was determined that patients with stage I or II gastric MALT lymphoma are able to undergo H. pylori eradication as a first-line treatment and that the survival rate of patients undergoing this treatment is high. Furthermore, it was determined that the mechanism by which miR-383 and ZEB2 contribute to MALT lymphoma progression is by the targeting of ZEB2 by miR-383, which inhibits the proliferation of cancer cells.

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Dysfunction of the Reciprocal Feedback Loop between GATA3- and ZEB2-Nucleated Repression Programs Contributes to Breast Cancer Metastasis

Cited by 134 publications

References 35 publications

The FOXN3-NEAT1-SIN3A repressor complex promotes progression of hormonally responsive breast cancer

The FOXN3-NEAT1-SIN3A repressor complex promotes progression of hormonally responsive breast cancer

ZEB1‐regulated inflammatory phenotype in breast cancer cells

Clinical manifestations and epigenetic mechanisms of gastric mucosa associated lymphoid tissue lymphoma and long‑term follow‑up following Helicobacterï¿½pylori eradication

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