Department of Head, Neck and Breast Surgery, Yue Bei People's Hospital, Shaoguan, Guangdong, China.
Chin J Physiol. 2022 Sep-Oct;65(5):233-240. doi: 10.4103/0304-4920.359800.
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.
骨髓间充质干细胞(BM-MSCs)具有自我更新和多能性的特性,能够通过释放外泌体迁移到肿瘤部位,并通过多种方式对肿瘤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展的影响。在这里,我们利用体外分离的 BM-MSCs 外泌体,在乳腺癌细胞系中系统地研究了这个问题。在这项研究中,我们发现 BM-MSCs 外泌体被乳腺癌细胞 MDA-MB-231 细胞主动摄取,并随后促进 MDA-MB-231 细胞的增殖和迁移。从机制上讲,我们进一步发现 Yes 相关蛋白(YAP)和转录共激活因子与 PDZ 结合基序(TAZ)是 Hippo 信号通路的组成部分,参与了这一促进过程。一致地,YAP 和 TAZ 的敲低可以显著逆转由 BM-MSCs 外泌体改善的乳腺癌细胞增殖和迁移。总之,我们的研究结果表明,BM-MSCs 衍生的外泌体可能通过一种新的机制促进乳腺癌细胞的增殖和迁移,这可能为基于外泌体和 Hippo 信号通路的新药发现提供依据。