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Disease models & mechanisms. 2024 Sep 1;17(9):dmm050771. doi: 10.1242/dmm.050771 Q13.32025

The highly metastatic 4T1 breast carcinoma model possesses features of a hybrid epithelial/mesenchymal phenotype

高转移性的4T1乳腺癌模型具有上皮间充质混合表型的特征 翻译改进

Mary E Herndon  1, Mitchell Ayers  2, Katherine N Gibson-Corley  3  4, Michael K Wendt  4  5, Lori L Wallrath  4  6, Michael D Henry  4  7, Christopher S Stipp  1  4  7

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作者单位

  • 1 Department of Biology, University of Iowa, Iowa City, IA 52245, USA.
  • 2 Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.
  • 3 Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • 4 Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA.
  • 5 Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
  • 6 Department of Biochemistry and Molecular Biology, University of Iowa, Iowa City, IA 52242, USA.
  • 7 Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, USA.
  • DOI: 10.1242/dmm.050771 PMID: 39104192

    摘要 中英对照阅读

    Epithelial-mesenchymal transitions (EMTs) are thought to promote metastasis via downregulation of E-cadherin (also known as Cdh1) and upregulation of mesenchymal markers such as N-cadherin (Cdh2) and vimentin (Vim). Contrary to this, E-cadherin is retained in many invasive carcinomas and promotes collective cell invasion. To investigate how E-cadherin regulates metastasis, we examined the highly metastatic, E-cadherin-positive murine 4T1 breast cancer mode... ...点击完成人机验证后继续浏览

    上皮-间质转化(EMT)被认为通过下调 E-钙黏蛋白(也称为 Cdh1)和上调如 N-钙黏蛋白(Cdh2)和波形蛋白(Vim)等间充质标志物来促进转移。相反,许多侵袭性癌细胞中保留了E-钙黏蛋白,并且它促进了集体细胞入侵。为了研究E-钙黏蛋白如何调节转移,我们检查了高转移性的、E-钙黏蛋白阳性的小鼠4T1乳腺癌模型,以及低转移性的、与4T1相关的细胞系4T07、168FARN和67NR。我们发现,4T1细胞表现出一种混合上皮/间充质表型,同时表达上皮和间充质标志物,而4T07、168FARN和67NR细胞在体外逐渐显示更倾向于间充质的表型,这与它们在体内转移能力呈负相关。使用RNA干扰和组成性表达技术,我们证明E-钙黏蛋白的表达水平并不决定4T1或4T07细胞的小鼠转移能力。从机制上讲,4T1细胞具有高度动态且不稳定的细胞间连接,并且可以在不下调E-钙黏蛋白的情况下进行集体入侵。然而,在体内正确定位的4T1肿瘤中也存在部分区域表现出EMT样丧失E-钙黏蛋白的现象。因此,4T1细胞作为一个模型用于研究混合上皮/间充质表型促进侵袭和转移的癌细胞。

    关键词:乳腺癌;集体迁移;E-钙黏蛋白;上皮-间充质转化;转移。

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    期刊名:Disease models & mechanisms

    缩写:DIS MODEL MECH

    ISSN:1754-8403

    e-ISSN:1754-8411

    IF/分区:3.3/Q1

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