Abstract:
BACKGROUND/AIM:Signaling regulation of myeloid zinc finger 1 (MZF1) has been implicated in the progression of many human malignancies; however, the mechanistic action of MZF1 in triple-negative breast cancer (TNBC) progression remains elusive. In this study, the aim was to investigate the molecular mechanisms of MZF1 and its functional role in TNBC cellular migration and invasion. MATERIALS AND METHODS:Hs578T and MDA-MB-231 cells were transfected to stably express the acidic domain of MZF1 (MZF160-72), or were transfected with MZF1-specific or ELK1-specific short hairpin RNA (shRNA). Changes in cell morphology and distributions of cellular proteins were observed and subsequently migration and invasion were measured by wound healing and transwell assays. Expression levels of epithelial-mesenchymal transition (EMT)-related genes were carried out using immunoblotting and quantitative reverse transcription-polymerase chain reaction (RT-PCR) assays. Data of transcriptional regulation were obtained from promoter-luciferase reporter and chromatin immunoprecipitation (ChIP) assays. RESULTS:Herein, we found that MZF1 in high-level MZF1-expressing TNBC cells is associated with cell migration, invasion, and mesenchymal phenotype. MZF1 interacted with the promoter region of insulin-like growth factor 1 receptor (IGF1R) to drive invasion and metastasis of high-level MZF1-expressing TNBC cells. Exogenous expression of the acidic domain of MZF1 repressed the binding of endogenous MZF1 to IGF1R promoter via blocking the interaction with ETS-like gene 1 (ELK1). This blockage not only caused MZF1 protein degradation, but also restrained ELK1 nuclear localization in high-level MZF1-expressing TNBC cells. MZF1, but not ELK1, was necessary for the retention of mesenchymal phenotype by repressing IGF1R promoter activity in TNBC cells expressing high levels of MZF1. Activation of the IGF1R-driven p38MAPK-ERα-slug-E-cadherin signaling axis mediated the conversion of mesenchymal cell to epithelial phenotype, caused by MZF1 destabilization. These results suggest that MZF1 is an oncogenic inducer. CONCLUSION:Blocking of the MZF1/ELK1 interaction to reduce MZF1 protein stability by saturating the endogenous MZF1/ELK1 binding domains might be a promising therapeutic strategy for the treatment of high-level MZF1-expressing TNBC.
journal_name
Anticancer Resjournal_title
Anticancer researchauthors
Yue CH,Liu JY,Chi CS,Hu CW,Tan KT,Huang FM,Pan YR,Lin KI,Lee CJdoi
10.21873/anticanres.13574subject
Has Abstractpub_date
2019-08-01 00:00:00pages
4149-4164issue
8eissn
0250-7005issn
1791-7530pii
39/8/4149journal_volume
39pub_type
杂志文章abstract:BACKGROUND:The tumors of the gastrointestinal system have been associated with various immune disorders. The goal of this study was to correlate the presence of the anti-dsDNA autoantibodies in the serum of patients with colorectal adenocarcinoma suffering from the prognosis of their disease. PATIENTS AND METHODS:We i...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2000-11-01 00:00:00
abstract::Intraosseous lipomas are rare benign primary bone tumors, with an incidence of one per thousand bone tumors. We studied eleven cases of intraosseous lipoma of the calcaneus. All the patients received radiographic examinations and MRI with T1-and T2-weighted images with Gd-DTPA enhancement. Seven patients received tumo...
journal_title:Anticancer research
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abstract::The significance of time interval for administration of a second drug after a first dose of cyclophosphamide (CTX) was studied for a human ovarian, lung, and colon carcinoma line growing as xenografts in nude mice. The effects of combination of two drugs were found to be dependent on the interval between the administr...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1985-03-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:10.21873/anticanres.14410
更新日期:2020-07-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2010-06-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1996-11-01 00:00:00
abstract::To identify retinoic acid (RA) signalling pathways involved in growth and differentiation in cells of the glial lineage, two human glioma ceh lines were studied. The three RA receptors (RARs) mRNAs were constitutively expressed, and of the three RXRs, RXR beta appeared predominant. Western blotting analysis confirmed ...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1999-07-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2012-04-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2006-07-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2008-11-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1998-07-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2003-03-01 00:00:00
abstract::A paclitaxel derivative was used for the preparation of a drug immunoconjugate for the specific targeting to ovarian cancer cells by the BCM43/2E5 monoclonal antibody. To determine the efficiency of conjugation we developed two reproducible immunoassays. Paclitaxel was detected on the conjugate by a paclitaxel immunoa...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2001-03-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2011-05-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2000-07-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2007-09-01 00:00:00
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journal_title:Anticancer research
pub_type: 临床试验,杂志文章
doi:
更新日期:2005-07-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2012-11-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:10.21873/anticanres.14009
更新日期:2020-02-01 00:00:00
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journal_title:Anticancer research
pub_type: 临床试验,杂志文章
doi:
更新日期:1995-11-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2006-11-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1998-07-01 00:00:00
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journal_title:Anticancer research
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更新日期:2019-06-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
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更新日期:2018-01-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2008-01-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2013-01-01 00:00:00
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journal_title:Anticancer research
pub_type: 临床试验,杂志文章
doi:
更新日期:1999-07-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1997-07-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章,meta分析
doi:
更新日期:2016-04-01 00:00:00
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pub_type: 杂志文章,评审
doi:
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