Zeb1 affects epithelial cell adhesion by diverting glycosphingolipid metabolism
Zeb1 affects epithelial cell adhesion by diverting glycosphingolipid metabolism
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DOI：
10.15252/embr.201439333
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发表时间：
2015-03-01
期刊：
影响因子：
7.7
通讯作者：
Feuerborn, Alexander
中科院分区：
文献类型：
--
作者：
Mathow, Daniel;Chessa, Federica;Feuerborn, Alexander
这项研究提出，转录因子Zeb 1调节上皮细胞粘附转移鞘糖脂代谢。Zeb 1通过调节GM 3合酶（St 3gal 5）的表达来促进a系列鞘糖脂的表达，其机制涉及Zeb 1与St 3gal 5启动子的结合以及抑制microRNA介导的St 3gal 5的抑制。在功能上，St 3gal 5的抑制足以提高细胞间粘附和不同连接相关蛋白的表达，这让人想起Zeb 1的敲除。相反，过表达St 3gal 5使细胞对TGF-β 1诱导的细胞-细胞相互作用的破坏敏感，并部分拮抗Zeb 1敲低引起的细胞间粘附的升高。这些结果突出了鞘糖脂代谢和上皮细胞粘附通过Zeb 1的直接连接。
This study proposes that the transcription factor Zeb1 modulates epithelial cell adhesion by diverting glycosphingolipid metabolism. Zeb1 promotes expression of a-series glycosphingolipids via regulating expression of GM3 synthase (St3gal5), which mechanistically involves Zeb1 binding to the St3gal5 promoter as well as suppressing microRNA-mediated repression of St3gal5. Functionally, the repression of St3gal5 suffices to elevate intercellular adhesion and expression of distinct junction-associated proteins, reminiscent of knockdown of Zeb1. Conversely, overexpressing St3gal5 sensitizes cells towards TGF-beta 1-induced disruption of cell-cell interaction and partially antagonizes elevation of intercellular adhesion imposed by Zeb1 knockdown. These results highlight a direct connection of glycosphingolipid metabolism and epithelial cell adhesion via Zeb1.