DRIM modulates Src activation and regulates angiogenic functions in vascular endothelial cells

Tong, Jia, Dong, Xuefei, Martin, Tracey A. ORCID: https://orcid.org/0000-0003-2690-4908, Yang, Yiming, Dong, Bo and Jiang, Wen ORCID: https://orcid.org/0000-0002-3283-1111 2025. DRIM modulates Src activation and regulates angiogenic functions in vascular endothelial cells. Cell Biology International 49 (3) , pp. 277-287. 10.1002/cbin.12265

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Publisher:	Wiley
ISSN:	1065-6995
Funders:	National Natural Science Foundation of China, Taishan Scholar Foundation of Shandong Province
Date of First Compliant Deposit:	3 December 2024
Date of Acceptance:	22 November 2024
Last Modified:	03 Mar 2025 14:19
URI:	https://orca.cardiff.ac.uk/id/eprint/174250

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