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

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 c...

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Autores principales:	Ke Shi, Jin Zhong Zhang, Liang Yang, Ning-Ning Li, Ying Yue, Xiu-Hong Du, Xiu-Zhi Zhang, Yu Cheng Lu, Dan Guo
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Aurora A USP3 Ubiquitination EMT Esophageal squamous cell carcinoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/d1128292aea34b7d89e20b01b1e11941
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spelling	oai:doaj.org-article:d1128292aea34b7d89e20b01b1e119412021-11-14T12:30:03ZProtein deubiquitylase USP3 stabilizes Aurora A to promote proliferation and metastasis of esophageal squamous cell carcinoma10.1186/s12885-021-08934-x1471-2407https://doaj.org/article/d1128292aea34b7d89e20b01b1e119412021-11-01T00:00:00Zhttps://doi.org/10.1186/s12885-021-08934-xhttps://doaj.org/toc/1471-2407Abstract 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.Ke ShiJin Zhong ZhangLiang YangNing-Ning LiYing YueXiu-Hong DuXiu-Zhi ZhangYu Cheng LuDan GuoBMCarticleAurora AUSP3UbiquitinationEMTEsophageal squamous cell carcinomaNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBMC Cancer, Vol 21, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Aurora A USP3 Ubiquitination EMT Esophageal squamous cell carcinoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Aurora A USP3 Ubiquitination EMT Esophageal squamous cell carcinoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Ke Shi Jin Zhong Zhang Liang Yang Ning-Ning Li Ying Yue Xiu-Hong Du Xiu-Zhi Zhang Yu Cheng Lu Dan Guo Protein deubiquitylase USP3 stabilizes Aurora A to promote proliferation and metastasis of esophageal squamous cell carcinoma
description	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.
format	article
author	Ke Shi Jin Zhong Zhang Liang Yang Ning-Ning Li Ying Yue Xiu-Hong Du Xiu-Zhi Zhang Yu Cheng Lu Dan Guo
author_facet	Ke Shi Jin Zhong Zhang Liang Yang Ning-Ning Li Ying Yue Xiu-Hong Du Xiu-Zhi Zhang Yu Cheng Lu Dan Guo
author_sort	Ke Shi
title	Protein deubiquitylase USP3 stabilizes Aurora A to promote proliferation and metastasis of esophageal squamous cell carcinoma
title_short	Protein deubiquitylase USP3 stabilizes Aurora A to promote proliferation and metastasis of esophageal squamous cell carcinoma
title_full	Protein deubiquitylase USP3 stabilizes Aurora A to promote proliferation and metastasis of esophageal squamous cell carcinoma
title_fullStr	Protein deubiquitylase USP3 stabilizes Aurora A to promote proliferation and metastasis of esophageal squamous cell carcinoma
title_full_unstemmed	Protein deubiquitylase USP3 stabilizes Aurora A to promote proliferation and metastasis of esophageal squamous cell carcinoma
title_sort	protein deubiquitylase usp3 stabilizes aurora a to promote proliferation and metastasis of esophageal squamous cell carcinoma
publisher	BMC
publishDate	2021
url	https://doaj.org/article/d1128292aea34b7d89e20b01b1e11941
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Protein deubiquitylase USP3 stabilizes Aurora A to promote proliferation and metastasis of esophageal squamous cell carcinoma

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