Protein deubiquitylase USP3 stabilizes Aurora A to promote proliferation and metastasis of esophageal squamous cell carcinoma

BMC Cancer

Yu Cheng Lu¹  Xiu-Zhi Zhang²  Ning-Ning Li²  Jin Zhong Zhang²  Ke Shi²  Xiu-Hong Du²  Dan Guo²  Liang Yang²  Ying Yue³ 

[1] Central Laboratory, Linyi People’s Hospital;Department of Biochemistry and Molecular Biology, Henan Medical College;Henan No.2 Provincial People’s Hospital, Henan Medical College Hospital Workers;

关键词: Aurora A;    USP3;    Ubiquitination;    EMT;    Esophageal squamous cell carcinoma;   

DOI  :  10.1186/s12885-021-08934-x

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown