文章：

四跨膜蛋白Tspan8与内皮素转换酶ECE1结合并调控其活性

The Tetraspanin Tspan8 Associates with Endothelin Converting Enzyme ECE1 and Regulates Its Activity

原文发布日期：27 September 2023

DOI: 10.3390/cancers15194751

类型: Article

开放获取: 是

英文摘要：

Tspan8 is a member of the tetraspanins family of cell surface molecules. The ability of tetraspanins to organize membrane microdomains with other membrane molecules and interfere with their function suggests that they could act as surface integrators of external or internal signals. Among the first identified tetraspanins, Tspan8 promotes tumor progression and metastasis, presumably by stimulating angiogenesis and cell motility. In patients, its expression on digestive tract tumors seems to be associated with a bad prognosis. We showed previously that Tspan8 associates with E-cadherin and EGFR and modulates their effects on cell motility. Using Mass spectrometry and western blot, we found a new partner, the endothelin converting enzyme ECE1, and showed that Tspan8 amplifies its activity of conversion of the endothelin-1 precursor bigET1 to endothelin. This was observed by transduction of the colon carcinoma cell line Isreco1, which does not express Tspan8, and on ileum tissue fragments of tspan8ko mice versus wild type mice. Given these results, Tspan8 appears to be a modulator of the endothelin axis, which could possibly be targeted in case of over-activity of endothelins in biological processes of tissues expressing Tspan8.

摘要翻译： 

Tspan8是四跨膜蛋白家族细胞表面分子的成员。四跨膜蛋白能够与其他膜分子共同组织膜微区并干扰其功能，这表明它们可能作为外部或内部信号的表面整合器。在最早被识别的四跨膜蛋白中，Tspan8通过刺激血管生成和细胞运动促进肿瘤进展和转移。在患者中，其在消化道肿瘤上的表达似乎与不良预后相关。我们先前的研究表明，Tspan8与E-钙黏蛋白和EGFR结合，并调节它们对细胞运动的影响。通过质谱分析和蛋白质印迹法，我们发现了一个新的相互作用蛋白——内皮素转换酶ECE1，并证明Tspan8能增强其将内皮素-1前体bigET1转化为内皮素的活性。这一现象在不表达Tspan8的结肠癌细胞系Isreco1中转导Tspan8后得到验证，并在tspan8基因敲除小鼠与野生型小鼠的回肠组织片段对比中得以证实。基于这些结果，Tspan8似乎是内皮素轴的调节因子，在表达Tspan8的组织中内皮素生物过程过度活跃时，可能成为潜在的治疗靶点。

原文链接：

The Tetraspanin Tspan8 Associates with Endothelin Converting Enzyme ECE1 and Regulates Its Activity