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

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 carci...

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Autores principales: Shi, Ke, Zhang, Jin Zhong, Yang, Liang, Li, Ning-Ning, Yue, Ying, Du, Xiu-Hong, Zhang, Xiu-Zhi, Lu, Yu Cheng, Guo, Dan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582154/
https://www.ncbi.nlm.nih.gov/pubmed/34758762
http://dx.doi.org/10.1186/s12885-021-08934-x
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author Shi, Ke
Zhang, Jin Zhong
Yang, Liang
Li, Ning-Ning
Yue, Ying
Du, Xiu-Hong
Zhang, Xiu-Zhi
Lu, Yu Cheng
Guo, Dan
author_facet Shi, Ke
Zhang, Jin Zhong
Yang, Liang
Li, Ning-Ning
Yue, Ying
Du, Xiu-Hong
Zhang, Xiu-Zhi
Lu, Yu Cheng
Guo, Dan
author_sort Shi, Ke
collection PubMed
description 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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spelling pubmed-85821542021-11-15 Protein deubiquitylase USP3 stabilizes Aurora A to promote proliferation and metastasis of esophageal squamous cell carcinoma Shi, Ke Zhang, Jin Zhong Yang, Liang Li, Ning-Ning Yue, Ying Du, Xiu-Hong Zhang, Xiu-Zhi Lu, Yu Cheng Guo, Dan BMC Cancer Research 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. BioMed Central 2021-11-10 /pmc/articles/PMC8582154/ /pubmed/34758762 http://dx.doi.org/10.1186/s12885-021-08934-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Shi, Ke
Zhang, Jin Zhong
Yang, Liang
Li, Ning-Ning
Yue, Ying
Du, Xiu-Hong
Zhang, Xiu-Zhi
Lu, Yu Cheng
Guo, Dan
Protein deubiquitylase USP3 stabilizes Aurora A to promote proliferation and metastasis of esophageal squamous cell carcinoma
title 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_short 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
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582154/
https://www.ncbi.nlm.nih.gov/pubmed/34758762
http://dx.doi.org/10.1186/s12885-021-08934-x
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