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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| Format: | Article |
| Language: | English |
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BMC
2021-11-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-021-08934-x |
| _version_ | 1819043740660006912 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-21T10:01:35Z |
| format | Article |
| id | doaj.art-d1128292aea34b7d89e20b01b1e11941 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-21T10:01:35Z |
| publishDate | 2021-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-d1128292aea34b7d89e20b01b1e119412022-12-21T19:07:55ZengBMCBMC Cancer1471-24072021-11-0121111310.1186/s12885-021-08934-xProtein deubiquitylase USP3 stabilizes Aurora A to promote proliferation and metastasis of esophageal squamous cell carcinomaKe Shi0Jin Zhong Zhang1Liang Yang2Ning-Ning Li3Ying Yue4Xiu-Hong Du5Xiu-Zhi Zhang6Yu Cheng Lu7Dan Guo8Department of Biochemistry and Molecular Biology, Henan Medical CollegeDepartment of Biochemistry and Molecular Biology, Henan Medical CollegeDepartment of Biochemistry and Molecular Biology, Henan Medical CollegeDepartment of Biochemistry and Molecular Biology, Henan Medical CollegeHenan No.2 Provincial People’s Hospital, Henan Medical College Hospital WorkersDepartment of Biochemistry and Molecular Biology, Henan Medical CollegeDepartment of Biochemistry and Molecular Biology, Henan Medical CollegeCentral Laboratory, Linyi People’s HospitalDepartment of Biochemistry and Molecular Biology, Henan Medical CollegeAbstract 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.https://doi.org/10.1186/s12885-021-08934-xAurora AUSP3UbiquitinationEMTEsophageal squamous cell carcinoma |
| spellingShingle | 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 BMC Cancer Aurora A USP3 Ubiquitination EMT 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 | Aurora A USP3 Ubiquitination EMT Esophageal squamous cell carcinoma |
| url | https://doi.org/10.1186/s12885-021-08934-x |
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