期刊
JOURNAL OF CELLULAR BIOCHEMISTRY
卷 119, 期 1, 页码 691-700出版社
WILEY
DOI: 10.1002/jcb.26232
关键词
AKT; breast cancer; invasion; UCH-L1
资金
- American Heart Association [12SDG12070174]
- National Heart, Lung, and Blood Institute [HL124122]
- National Cancer Institute [CA109371]
- National Natural Science Foundation of China [81401155]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases [AR067766]
As a de-ubiquitin enzyme, ubiquitin C-terminal hydrolase (UCH)-L1 has been shown to be overexpressed in several human cancers. However, the function of UCH-L1 in invasion of breast cancers is still unclear. Here we report that the expression of UCH-L1 is significantly higher in cancer cells with higher invasive ability. While ectopic UCH-L1 expression failed to alter cell proliferation in MCF-7 cells, it caused a significant upregulation of cellular invasion. Furthermore, siRNA mediated knockdown of UCH-L1 led to suppression of invasion in UCH-L1 overexpressing MCF-7 cells. In order to identify molecular mechanisms underlying these observations, a novel in vitro proximity-dependent biotin identification method was developed by fusing UCH-L1 protein with a bacterial biotin ligase (Escherichia coli BirA R118G, BioID). Streptavidin magnetic beads pulldown assay revealed that UCH-L1 can interact with Akt in MCF-7 cells. Pulldown assay with His tagged recombinant UCH-L1 protein and cell lysate from MCF-7 cells further demonstrated that UCH-L1 preferentially binds to Akt2 for Akt activation. Finally, we demonstrated that overexpression of UCH-L1 led to activation of Akt as evidenced by upregulation of phosphorylated Akt. Thus, these findings demonstrated that UCH-L1 promotes invasion of breast cancer cells and might serve as a potential therapeutic target for treatment of human patients with breast cancers.
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