Jia Tong, Xuefei Dong, Tracey A Martin, Yiming Yang, Bo Dong, Wen G Jiang
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引用次数: 0
Abstract
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.
期刊介绍:
Each month, the journal publishes easy-to-assimilate, up-to-the minute reports of experimental findings by researchers using a wide range of the latest techniques. Promoting the aims of cell biologists worldwide, papers reporting on structure and function - especially where they relate to the physiology of the whole cell - are strongly encouraged. Molecular biology is welcome, as long as articles report findings that are seen in the wider context of cell biology. In covering all areas of the cell, the journal is both appealing and accessible to a broad audience. Authors whose papers do not appeal to cell biologists in general because their topic is too specialized (e.g. infectious microbes, protozoology) are recommended to send them to more relevant journals. Papers reporting whole animal studies or work more suited to a medical journal, e.g. histopathological studies or clinical immunology, are unlikely to be accepted, unless they are fully focused on some important cellular aspect.
These last remarks extend particularly to papers on cancer. Unless firmly based on some deeper cellular or molecular biological principle, papers that are highly specialized in this field, with limited appeal to cell biologists at large, should be directed towards journals devoted to cancer, there being very many from which to choose.