• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

锌指蛋白E盒结合因子1（ZEB1）通过靶向神经生成素-3赋予乳腺癌干细胞样特性。

ZEB1 confers stem cell-like properties in breast cancer by targeting neurogenin-3.

作者信息

Zhou Chen, Jiang Huimin, Zhang Zhen, Zhang Guomin, Wang Hang, Zhang Quansheng, Sun Peiqing, Xiang Rong, Yang Shuang

机构信息

Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Medical School of Nankai University, Tianjin 300071, China.

Tianjin Key Laboratory of Organ Transplantation, Tianjin First Center Hospital, Tianjin 300192, China.

出版信息

Oncotarget. 2017 Apr 13;8(33):54388-54401. doi: 10.18632/oncotarget.17077. eCollection 2017 Aug 15.

DOI:10.18632/oncotarget.17077
PMID:28903350
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5589589/
Abstract

Cancer stem cells (CSCs) are a subpopulation of cancer cells believed to be implicated in cancer initiation, progression, and recurrence. Here, we report that ectopic expression of zinc finger E-box binding homeobox 1 protein (ZEB1) results in the acquisition of CSC properties by breast cancer cells, leading to tumor initiation and progression and . The neurogenin 3 gene () is a bona fide target of ZEB1, and its repression is a key factor contributing to ZEB1-induced cancer cell stemness. ZEB1 suppressed transcription by forming a ZEB1/DNA methyltransferase (DNMT)3B/histone deacetylase 1 (HDAC1) complex on the promoter, leading to promoter hypermethylation and gene silencing. The rescue of expression attenuated ZEB1-induced cancer stemness and symmetric CSC division. Immunohistological analysis of human breast cancer specimens revealed a strong inverse relationship between ZEB1 and NGN3 protein expression. Thus, our findings suggest ZEB1-mediated silencing of is required for breast tumor initiation and maintenance. Targeted therapies against the ZEB1/Ngn3 axis may be highly valuable for the prevention and treatment of breast cancer.

摘要

癌症干细胞（CSCs）是癌细胞的一个亚群，被认为与癌症的发生、发展和复发有关。在此，我们报告锌指E盒结合同源框1蛋白（ZEB1）的异位表达导致乳腺癌细胞获得CSC特性，从而引发肿瘤起始和进展。神经生成素3基因（）是ZEB1的一个真正靶点，其抑制是导致ZEB1诱导的癌细胞干性的关键因素。ZEB1通过在启动子上形成ZEB1/DNA甲基转移酶（DNMT）3B/组蛋白去乙酰化酶1（HDAC1）复合物来抑制转录，导致启动子高甲基化和基因沉默。表达的挽救减弱了ZEB1诱导的癌症干性和对称CSC分裂。对人类乳腺癌标本的免疫组织学分析显示，ZEB1与NGN3蛋白表达之间存在强烈的负相关关系。因此，我们的研究结果表明，ZEB1介导的沉默对于乳腺肿瘤的起始和维持是必需的。针对ZEB1/Ngn3轴的靶向治疗可能对乳腺癌的预防和治疗具有很高的价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2165/5589589/713875c892cf/oncotarget-08-54388-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2165/5589589/81198a3f2cb6/oncotarget-08-54388-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2165/5589589/efc7bde40d10/oncotarget-08-54388-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2165/5589589/322cfb648d86/oncotarget-08-54388-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2165/5589589/8d7920631854/oncotarget-08-54388-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2165/5589589/f80d06dc617b/oncotarget-08-54388-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2165/5589589/713875c892cf/oncotarget-08-54388-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2165/5589589/81198a3f2cb6/oncotarget-08-54388-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2165/5589589/efc7bde40d10/oncotarget-08-54388-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2165/5589589/322cfb648d86/oncotarget-08-54388-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2165/5589589/8d7920631854/oncotarget-08-54388-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2165/5589589/f80d06dc617b/oncotarget-08-54388-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2165/5589589/713875c892cf/oncotarget-08-54388-g006.jpg

相似文献

1
ZEB1 confers stem cell-like properties in breast cancer by targeting neurogenin-3.锌指蛋白E盒结合因子1（ZEB1）通过靶向神经生成素-3赋予乳腺癌干细胞样特性。
Oncotarget. 2017 Apr 13;8(33):54388-54401. doi: 10.18632/oncotarget.17077. eCollection 2017 Aug 15.
2
ZEB1 induces ER-α promoter hypermethylation and confers antiestrogen resistance in breast cancer.ZEB1诱导雌激素受体α（ER-α）启动子高甲基化并赋予乳腺癌抗雌激素耐药性。
Cell Death Dis. 2017 Apr 6;8(4):e2732. doi: 10.1038/cddis.2017.154.
3
The miR-200b-ZEB1 circuit regulates diverse stemness of human hepatocellular carcinoma.miR-200b-ZEB1 信号通路调控人肝细胞癌的多种干性。
Mol Carcinog. 2017 Sep;56(9):2035-2047. doi: 10.1002/mc.22657. Epub 2017 Apr 18.
4
Knockdown of ZEB1 reverses cancer stem cell properties in prostate cancer cells.敲低 ZEB1 逆转前列腺癌细胞中的癌症干细胞特性。
Oncol Rep. 2021 May;45(5). doi: 10.3892/or.2021.8009. Epub 2021 Mar 24.
5
Zinc-finger E-box-binding homeobox 1 (ZEB1) plays a crucial role in the maintenance of lung cancer stem cells resistant to gefitinib.锌指 E-box 结合同源盒 1（ZEB1）在维持对吉非替尼耐药的肺癌干细胞中发挥着关键作用。
Thorac Cancer. 2021 May;12(10):1536-1548. doi: 10.1111/1759-7714.13937. Epub 2021 Mar 25.
6
Decrease of ZEB1 expression inhibits the B16F10 cancer stem-like properties.ZEB1表达的降低抑制了B16F10癌症干细胞样特性。
Biosci Trends. 2015 Oct;9(5):325-34. doi: 10.5582/bst.2015.01106.
7
Downregulation of DAPK1 promotes the stemness of cancer stem cells and EMT process by activating ZEB1 in colorectal cancer.下调 DAPK1 通过激活结直肠癌中的 ZEB1 促进癌症干细胞的干性和 EMT 过程。
J Mol Med (Berl). 2019 Jan;97(1):89-102. doi: 10.1007/s00109-018-1716-8. Epub 2018 Nov 20.
8
Jagged1-Notch1-deployed tumor perivascular niche promotes breast cancer stem cell phenotype through Zeb1.锯齿状 1-Notch1 靶向的肿瘤血管周龛促进乳腺癌干细胞表型通过 Zeb1。
Nat Commun. 2020 Oct 12;11(1):5129. doi: 10.1038/s41467-020-18860-4.
9
ZEB1 potentiates chemoresistance in breast cancer stem cells by evading apoptosis.ZEB1通过逃避凋亡增强乳腺癌干细胞的化疗耐药性。
Biochim Biophys Acta Mol Cell Res. 2023 Oct;1870(7):119528. doi: 10.1016/j.bbamcr.2023.119528. Epub 2023 Jun 23.
10
Epithelial-mesenchymal transition transcription factor ZEB1/ZEB2 co-expression predicts poor prognosis and maintains tumor-initiating properties in head and neck cancer.上皮-间充质转化转录因子 ZEB1/ZEB2 共表达预测头颈部癌症预后不良，并维持肿瘤起始特性。
Oral Oncol. 2013 Jan;49(1):34-41. doi: 10.1016/j.oraloncology.2012.07.012. Epub 2012 Aug 11.

引用本文的文献

1
Differential Effects of Snail-KO in Human Breast Epithelial Cells and Human Breast Epithelial × Human Breast Cancer Hybrids.蜗牛基因敲除对人乳腺上皮细胞和人乳腺上皮×人乳腺癌杂交细胞的不同影响。
Int J Mol Sci. 2025 Jul 22;26(15):7033. doi: 10.3390/ijms26157033.
2
Strictosamide and mitraphylline inhibit cancer cell motility by suppressing epithelial-mesenchymal transition via integrin α4-mediated signaling.Strictosamide和Mitraphylline通过整合素α4介导的信号通路抑制上皮-间质转化，从而抑制癌细胞的迁移。
Sci Rep. 2025 Jul 2;15(1):22807. doi: 10.1038/s41598-025-04064-7.
3
Polo-like Kinase 1 Predicts Lymph Node Metastasis in Middle Eastern Colorectal Cancer Patients; Its Inhibition Reverses 5-Fu Resistance in Colorectal Cancer Cells.

本文引用的文献

1
The linker histone H1.0 generates epigenetic and functional intratumor heterogeneity.连接组蛋白H1.0产生表观遗传和功能性肿瘤内异质性。
Science. 2016 Sep 30;353(6307). doi: 10.1126/science.aaf1644.
2
Nesfatin-1/Nucleobindin-2 enhances cell migration, invasion, and epithelial-mesenchymal transition via LKB1/AMPK/TORC1/ZEB1 pathways in colon cancer.在结肠癌中，Nesfatin-1/核结合蛋白-2通过LKB1/AMPK/TORC1/ZEB1信号通路增强细胞迁移、侵袭及上皮-间质转化。
Oncotarget. 2016 May 24;7(21):31336-49. doi: 10.18632/oncotarget.9140.
3
ZEB1 turns into a transcriptional activator by interacting with YAP1 in aggressive cancer types.
Polo-like Kinase 1 预测中东结直肠癌患者的淋巴结转移；其抑制作用可逆转结直肠癌细胞对 5-Fu 的耐药性。
Cells. 2024 Oct 14;13(20):1700. doi: 10.3390/cells13201700.
4
Altered Phenotypes of Breast Epithelial × Breast Cancer Hybrids after ZEB1 Knock-Out.ZEB1 基因敲除后乳腺上皮×乳腺癌杂交细胞表型的改变。
Int J Mol Sci. 2023 Dec 9;24(24):17310. doi: 10.3390/ijms242417310.
5
LINC01806 Promotes Breast Cancer Growth and Metastasis via Sponging miR-1286 to Disinhibit ZEB1 Expression.LINC01806通过吸附miR-1286解除对ZEB1表达的抑制来促进乳腺癌的生长和转移。
Biochem Genet. 2024 Jun;62(3):1977-1993. doi: 10.1007/s10528-023-10507-5. Epub 2023 Oct 9.
6
Epigenetically upregulating TROP2 and SLFN11 enhances therapeutic efficacy of TROP2 antibody drug conjugate sacitizumab govitecan.通过表观遗传上调TROP2和SLFN11可增强TROP2抗体药物偶联物戈沙妥珠单抗的治疗效果。
NPJ Breast Cancer. 2023 Aug 11;9(1):66. doi: 10.1038/s41523-023-00573-8.
7
MiR-662 is associated with metastatic relapse in early-stage breast cancer and promotes metastasis by stimulating cancer cell stemness.miR-662 与早期乳腺癌的转移复发相关，并通过刺激癌细胞干性促进转移。
Br J Cancer. 2023 Sep;129(5):754-771. doi: 10.1038/s41416-023-02340-9. Epub 2023 Jul 13.
8
p53 Affects Zeb1 Interactome of Breast Cancer Stem Cells.p53 影响乳腺癌干细胞的 Zeb1 相互作用组。
Int J Mol Sci. 2023 Jun 6;24(12):9806. doi: 10.3390/ijms24129806.
9
Dissecting the effects of androgen deprivation therapy on cadherin switching in advanced prostate cancer: A molecular perspective.剖析雄激素剥夺疗法对晚期前列腺癌钙黏蛋白转换的影响：分子视角。
Oncol Res. 2023 Jan 12;30(3):137-155. doi: 10.32604/or.2022.026074. eCollection 2022.
10
Synthetic Epigenetic Reprogramming of Mesenchymal to Epithelial States Using the CRISPR/dCas9 Platform in Triple Negative Breast Cancer.利用 CRISPR/dCas9 平台在三阴性乳腺癌中对间充质到上皮状态进行合成表观遗传重编程。
Adv Sci (Weinh). 2023 Aug;10(22):e2301802. doi: 10.1002/advs.202301802. Epub 2023 May 22.
在侵袭性癌症类型中，ZEB1通过与YAP1相互作用转变为转录激活因子。
Nat Commun. 2016 Feb 15;7:10498. doi: 10.1038/ncomms10498.
4
The Numb/p53 circuitry couples replicative self-renewal and tumor suppression in mammary epithelial cells.Numb/p53信号通路在乳腺上皮细胞中连接了复制性自我更新与肿瘤抑制。
J Cell Biol. 2015 Nov 23;211(4):845-62. doi: 10.1083/jcb.201505037.
5
Control of stem cell self-renewal and differentiation by the heterochronic genes and the cellular asymmetry machinery in Caenorhabditis elegans.秀丽隐杆线虫中异时性基因和细胞不对称机制对干细胞自我更新和分化的调控
Proc Natl Acad Sci U S A. 2015 Jan 20;112(3):E287-96. doi: 10.1073/pnas.1422852112. Epub 2015 Jan 5.
6
Role of p53 in the progression of gastric cancer.p53在胃癌进展中的作用。
Oncotarget. 2014 Dec 15;5(23):12016-26. doi: 10.18632/oncotarget.2434.
7
Systematically labeling developmental stage-specific genes for the study of pancreatic β-cell differentiation from human embryonic stem cells.系统地标记发育阶段特异性基因，用于研究人胚胎干细胞向胰腺β细胞的分化。
Cell Res. 2014 Oct;24(10):1181-200. doi: 10.1038/cr.2014.118. Epub 2014 Sep 5.
8
ATM-mediated stabilization of ZEB1 promotes DNA damage response and radioresistance through CHK1.ATM介导的ZEB1稳定通过CHK1促进DNA损伤反应和放射抗性。
Nat Cell Biol. 2014 Sep;16(9):864-75. doi: 10.1038/ncb3013. Epub 2014 Aug 3.
9
MicroRNA-205 signaling regulates mammary stem cell fate and tumorigenesis.微小RNA-205信号传导调节乳腺干细胞命运和肿瘤发生。
J Clin Invest. 2014 Jul;124(7):3093-106. doi: 10.1172/JCI73351. Epub 2014 Jun 9.
10
Expression pattern of Ngn3 in dairy goat testis and its function in promoting meiosis by upregulating Stra8.Ngn3 在奶山羊睾丸中的表达模式及其通过上调 Stra8 促进减数分裂的功能
Cell Prolif. 2014 Feb;47(1):38-47. doi: 10.1111/cpr.12077. Epub 2013 Nov 29.