1. Protein deubiquitylase USP3 stabilizes Aurora A to promote proliferation and metastasis of esophageal squamous cell carcinoma
- Author
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Ke Shi, Jin Zhong Zhang, Ying Yue, Ning-Ning Li, Yu Cheng Lu, Dan Guo, Xiu-Zhi Zhang, Liang Yang, and Xiu-Hong Du
- Subjects
Proteasome Endopeptidase Complex ,Cancer Research ,Esophageal Neoplasms ,Carcinogenesis ,Aurora A kinase ,macromolecular substances ,Biology ,Esophageal squamous cell carcinoma ,Metastasis ,Ubiquitin ,Surgical oncology ,Cell Line, Tumor ,Genetics ,medicine ,Humans ,Aurora A ,Kinase activity ,Proteasome degradation ,RC254-282 ,Aurora Kinase A ,Cell Proliferation ,Research ,Ubiquitination ,EMT ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,digestive system diseases ,Gene Expression Regulation, Neoplastic ,enzymes and coenzymes (carbohydrates) ,Oncology ,USP3 ,Proteolysis ,embryonic structures ,Cancer research ,biology.protein ,Ubiquitin-Specific Proteases ,biological phenomena, cell phenomena, and immunity ,Deubiquitination - Abstract
Aurora A kinase is a cell cycle regulator that is dysregulated in several different malignancies. Nevertheless, its regulatory mechanisms are still not fully understood. Here, we report that ubiquitin specific peptidase 3 (USP3) promotes proliferation and metastasis of esophageal squamous cell carcinoma (ESCC) cells by mediating deubiquitination of Aurora A. Analysis of human clinical samples indicated that USP3 and Aurora A are highly expressed in ESCC. Cellular experiments confirmed that high expression of USP3 and Aurora A in ESCC cells promoted malignant cell proliferation and invasion. In this mechanism, USP3 leads to suppression of Aurora A ubiquitination, resulting less proteasome degradation. We constructed the deubiquitinated mimetic K143R of Aurora A and found that K143R significantly promoted the proliferation and invasion of ESCC cells and was not regulated by the deubiquitination of USP3. Moreover, Aurora A K143R potentiated the kinase activity of Aurora A in ESCC cells. Thus, our findings demonstrate that the tumorigenic feature of ESCC is in part mediated by USP3-facilitated deubiquitination of Aurora A.
- Published
- 2021