来自骨髓间充质干细胞的外泌体通过上调乳腺癌细胞中蛋白相关蛋白/ PDZ结合基序的转录共激活因子的表达来促进增殖和迁移。

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Wanming Wu, Renfeng Huang, Linyang Ou, Ruiwen Lei
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引用次数: 1

摘要

骨髓间充质干细胞(Bone marrow mesenchymal stem cells, BM-MSCs)具有自我更新和多能性的特性,可以通过释放外泌体迁移到肿瘤部位,对肿瘤的进展和通讯发挥复杂的作用。然而,据我们所知,只有少数研究报道了BM-MSCs外泌体对乳腺癌细胞发育的影响。在这里,我们利用从体外BM-MSCs中分离的外泌体,系统地研究了乳腺癌细胞系的这一问题。在本研究中,我们发现BM-MSCs外泌体被乳腺癌细胞MDA-MB-231细胞积极结合,并随后促进MDA-MB-231细胞的增殖和迁移。在机制上,我们进一步发现yes相关蛋白(YAP)和带PDZ结合基序的转录共激活因子(TAZ)参与了这一促进过程。同样,YAP和TAZ敲低可以显著逆转BM-MSCs外泌体改善的乳腺癌细胞增殖和迁移。综上所述,我们的研究结果揭示了一种新的机制,通过这种机制,bm - mscs衍生的外泌体可能有助于乳腺癌细胞的增殖和迁移,这可能为基于外泌体和Hippo信号的新药开发提供证据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Exosomes derived from bone marrow mesenchymal stem cells promote proliferation and migration via upregulation yes-associated protein/transcriptional coactivator with PDZ binding motif expression in breast cancer cells.

Bone marrow mesenchymal stem cells (BM-MSCs), with the properties of self-renewal and pluripotency, can migrate to the tumor sites and exert complex effects on tumor progression and communications by releasing exosomes. However, to our knowledge, only a few studies have reported the effects of BM-MSCs exosomes on breast cancer cells development. Here, utilizing exosomes isolated from in vitro BM-MSCs, we systematically investigated this issue in a breast cancer cell line. In this study, we found that BM-MSCs exosomes are actively incorporated by breast cancer cell MDA-MB-231 cells and subsequently promote MDA-MB-231 cells proliferation and migration. Mechanistically, we further found Yes-associated protein (YAP) and transcriptional coactivator with PDZ binding motif (TAZ) which are Hippo signaling components were involved in this promoting progress. Consistently, YAP and TAZ knockdown could significantly reverse breast cancer cells proliferation and migration improved by BM-MSCs exosomes. Taken together, our findings demonstrated a new mechanism through which BM-MSCs-derived exosomes may contribute to breast cancer cells proliferation and migration, which might provide an evidence for novel drug discovery based on exosomes and Hippo signaling.

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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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