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Open Access 01-12-2021 | Metastasis | Research

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

Authors: Ke Shi, Jin Zhong Zhang, Liang Yang, Ning-Ning Li, Ying Yue, Xiu-Hong Du, Xiu-Zhi Zhang, Yu Cheng Lu, Dan Guo

Published in: BMC Cancer | Issue 1/2021

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.

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Title: Protein deubiquitylase USP3 stabilizes Aurora A to promote proliferation and metastasis of esophageal squamous cell carcinoma
Authors: Ke Shi
Jin Zhong Zhang
Liang Yang
Ning-Ning Li
Ying Yue
Xiu-Hong Du
Xiu-Zhi Zhang
Yu Cheng Lu
Dan Guo
Publication date: 01-12-2021
Publisher: BioMed Central
Keyword: Metastasis
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08934-x

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