Laboratory of Cell Engineering, Beijing Institute of Biotechnology (BIB), No. 20, Dongdajie Street, Fengtai District, Beijing, 100071, China.
Department of Operational Medicine, Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, China.
Cell Commun Signal. 2018 Sep 21;16(1):62. doi: 10.1186/s12964-018-0272-8.
TEM8 is a cell membrane protein predominantly expressed in tumor endothelium, which serves as a receptor for the protective antigen (PA) of anthrax toxin. However, the physiological ligands for TEM8 remain unknown.
Here we identified uPA as an interacting partner of TEM8. Binding of uPA stimulated the phosphorylation of TEM8 and augmented phosphorylation of EGFR and ERK1/2. Finally, TEM8-Fc, a recombinant fusion protein comprising the extracellular domain of human TEM8 linked to the Fc portion of human IgG1, efficiently abrogated the interaction between uPA and TEM8, blocked uPA-induced migration of HepG2 cells in vitro and inhibited the growth and metastasis of human MCF-7 xenografts in vivo. uPA, TEM8 and EGFR overexpression and ERK1/2 phosphorylation were found co-located on frozen cancer tissue sections.
Taken together, our data provide evidence that TEM8 is a novel receptor for uPA, which may play a significant role in the regulation of tumor growth and metastasis.
TEM8 是一种主要表达于肿瘤内皮细胞的细胞膜蛋白，作为炭疽毒素保护性抗原（PA）的受体。然而，TEM8 的生理配体仍不清楚。
在这里，我们鉴定出 uPA 是 TEM8 的一个相互作用伙伴。uPA 的结合刺激了 TEM8 的磷酸化，并增强了 EGFR 和 ERK1/2 的磷酸化。最后，TEM8-Fc，一种由人 TEM8 的胞外结构域与 IgG1 的 Fc 部分相连的重组融合蛋白，有效地阻断了 uPA 与 TEM8 之间的相互作用，阻断了 uPA 诱导的 HepG2 细胞在体外的迁移，并抑制了人 MCF-7 异种移植瘤在体内的生长和转移。uPA、TEM8 和 EGFR 的过表达和 ERK1/2 的磷酸化在冷冻的癌组织切片上共定位。
总之，我们的数据提供了证据表明 TEM8 是 uPA 的一个新受体，它可能在肿瘤生长和转移的调节中发挥重要作用。
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