邻苯二甲酸丁基苄基酯 (BBP) 通过上调 Zeb1 触发血管瘤细胞的迁移和侵袭。
Benzyl butyl phthalate (BBP) triggers the migration and invasion of hemangioma cells via upregulation of Zeb1.
机构信息
Department of Microsurgery, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China.
Luoyang Vocational and Technical College, Luoyang 471003, China.
出版信息
Toxicol In Vitro. 2019 Oct;60:323-329. doi: 10.1016/j.tiv.2019.06.013. Epub 2019 Jun 15.
Hemangioma (HA) are tumors formed by hyper-proliferation of vascular endothelial cells. As a potential endocrine disrupting chemical (EDC), benzyl butyl phthalate (BBP) can mimic estrogen to disturb the estrogenic signals. Our present study investigated the potential roles of phthalates on the progression of HA and found that 100 nM BBP can significantly trigger the migration and invasion of HA cells, which was evidenced by the results that BBP can induce the expression of matrix metalloproteinase (MMPs) and vimentin. Further, BBP can increase the expression of Zeb1, one powerful transcription factor for cell migration and invasion. Targeted inhibition of Zeb1 blocked BBP induced cell migration. Mechanistically, BBP can increase the mRNA stability of Zeb1 via suppression of miR-655. Further, BBP can enhance the protein stability of Zeb1 via upregulation of ataxia telangiectasia mutated (ATM). Collectively, our present study revealed that BBP can trigger the migration and invasion of HA cells via upregulation of Zeb1.
血管瘤 (HA) 是由血管内皮细胞过度增殖形成的肿瘤。作为一种潜在的内分泌干扰化学物质 (EDC)，邻苯二甲酸苄丁酯 (BBP) 可以模拟雌激素，扰乱雌激素信号。本研究探讨了邻苯二甲酸酯对 HA 进展的潜在作用，发现 100 nM BBP 可显著触发 HA 细胞的迁移和侵袭，这一结果表明 BBP 可诱导基质金属蛋白酶 (MMPs) 和波形蛋白的表达。此外，BBP 可增加 Zeb1 的表达，Zeb1 是细胞迁移和侵袭的强大转录因子之一。靶向抑制 Zeb1 可阻断 BBP 诱导的细胞迁移。在机制上，BBP 通过抑制 miR-655 增加 Zeb1 的 mRNA 稳定性。此外，BBP 通过上调共济失调毛细血管扩张突变 (ATM) 增加 Zeb1 的蛋白稳定性。总之，本研究揭示了 BBP 可通过上调 Zeb1 触发 HA 细胞的迁移和侵袭。
Zotero 插件