Tong Jia, Dong Xuefei, Martin Tracey A, Yang Yiming, Dong Bo, Jiang Wen G
Department of Geriatric Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong First Medical University, Jinan, China.
Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, UK.
Cell Biol Int. 2025 Mar;49(3):277-287. doi: 10.1002/cbin.12265. Epub 2024 Dec 8.
Downregulated in Metastasis Protein (DRIM) was discovered in malignant epithelial cells and was thought to be mainly a nucleus protein affecting cancer cells. Recent single-cell sequencing analysis suggests that DRIM is abundantly expressed in vascular endothelial cells. There has been no knowledge of the role of DRIM in the endothelium. In the present study, using protein fraction method and cell imaging, we identified that the DRIM protein was abundantly present in both nucleus and the cytoskeletal fractions of human vascular endothelial cells. Knockdown of DRIM in the endothelial cells significantly affected growth, migration, and angiogenic tubule formation. Proteomics analyses revealed that Src was an important direct target protein of DRIM, a finding further confirmed by protein interaction assay. Silencing DRIM activated the tyrosine 419 site phosphorylation of Src kinase in endothelial cells, thereby affecting the downstream proteins of Src including p-FAK and p-STAT3, and exerting biological effects. To conclude, our results provide evidence of DRIM being a nuclear and cytoskeletal-associated protein, having a novel key role of the protein in vascular endothelial cells.
转移下调蛋白（DRIM）是在恶性上皮细胞中发现的，曾被认为主要是一种影响癌细胞的核蛋白。最近的单细胞测序分析表明，DRIM在血管内皮细胞中大量表达。目前尚不清楚DRIM在内皮细胞中的作用。在本研究中，我们采用蛋白质分级分离法和细胞成像技术，确定DRIM蛋白在人血管内皮细胞的细胞核和细胞骨架组分中均大量存在。在内皮细胞中敲低DRIM会显著影响细胞生长、迁移和血管生成小管的形成。蛋白质组学分析显示，Src是DRIM的一个重要直接靶蛋白，蛋白质相互作用分析进一步证实了这一发现。沉默DRIM会激活内皮细胞中Src激酶的酪氨酸419位点磷酸化，从而影响Src的下游蛋白，包括p-FAK和p-STAT3，并发挥生物学效应。总之，我们的结果证明DRIM是一种与细胞核和细胞骨架相关的蛋白，该蛋白在血管内皮细胞中具有新的关键作用。
