Endothelial specific YY1 deletion restricts tumor angiogenesis and tumor growth.
Endothelial specific YY1 deletion restricts tumor angiogenesis and tumor growth.
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DOI：
10.1038/s41598-020-77568-z
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发表时间：
2020-11-24
影响因子：
4.6
通讯作者：
Jin ZG
中科院分区：
文献类型：
--
作者：
Liu H;Qiu Y;Pei X;Chitteti R;Steiner R;Zhang S;Jin ZG
血管生成是一种从原有血管生成新血管的生理过程，它在肿瘤的生存和生长中起着至关重要的作用。在肿瘤血管生成过程中，血管内皮细胞（EC）中基因转录因子的激活在促进EC增殖、迁移和血管网发育中起着至关重要的作用。然而，EC和肿瘤血管生成的转录调控的分子机制仍有待充分阐明。在这里，我们报告的转录因子阴阳1（YY 1）在内皮细胞是至关重要的参与肿瘤血管生成。首先，我们利用他莫昔芬诱导的EC特异性YY 1缺陷小鼠模型，并表明在EC中YY 1缺失抑制肿瘤生长和肿瘤血管生成。使用体内基质胶塞测定，我们发现EC特异性YY1消融抑制生长因子诱导的血管生成。此外，血管内皮生长因子（VEGF）诱导的EC迁移减少YY 1耗尽的人脐静脉内皮细胞（HUVECs）。最后，拯救实验表明，YY1调控的BMP 6在EC中的表达参与EC迁移。总的来说，我们的研究结果表明，内皮细胞YY1在肿瘤血管生成中起着至关重要的作用，并表明靶向内皮细胞YY1可能是一种潜在的癌症治疗策略。
Angiogenesis is a physiological process for the formation of new blood vessels from the pre-existing vessels and it has a vital role in the survival and growth of neoplasms. During tumor angiogenesis, the activation of the gene transcriptions in vascular endothelial cells (ECs) plays an essential role in the promotion of EC proliferation, migration, and vascular network development. However, the molecular mechanisms underlying transcriptional regulation of EC and tumor angiogenesis remains to be fully elucidated. Here we report that the transcription factor Yin Yang 1 (YY1) in ECs is critically involved in tumor angiogenesis. First, we utilized a tamoxifen-inducible EC-specific YY1 deficient mouse model and showed that YY1 deletion in ECs inhibited the tumor growth and tumor angiogenesis. Using the in vivo matrigel plug assay, we then found that EC-specific YY1 ablation inhibited growth factor-induced angiogenesis. Furthermore, vascular endothelial growth factor (VEGF)-induced EC migration was diminished in YY1-depleted human umbilical vein endothelial cells (HUVECs). Finally, a rescue experiment revealed that YY1-regulated BMP6 expression in ECs was involved in EC migration. Collectively, our results demonstrate that endothelial YY1 has a crucial role in tumor angiogenesis and suggest that targeting endothelial YY1 could be a potential therapeutic strategy for cancer treatment.
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DOI：
10.1016/j.trsl.2016.05.003
发表时间：
2016-10
期刊：
Translational research : the journal of laboratory and clinical medicine
影响因子：
--
作者：
Xu S;Koroleva M;Yin M;Jin ZG
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Jin ZG
影响因子：
1.3
作者：
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Ruegg, Curzio
影响因子：
29
作者：
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Scorrano, Luca
影响因子：
2.5
作者：
Monvoisin, Arnaud;Alva, Jackelyn A.;Iruela-Arispe, M. Luisa
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Iruela-Arispe, M. Luisa
DOI：
10.1073/pnas.1205526109
发表时间：
2012-08-21
影响因子：
11.1
作者：
Margariti, Andriana;Winkler, Bernhard;Xu, Qingbo
通讯作者：
Xu, Qingbo