USP26 promotes anaplastic thyroid cancer progression by stabilizing TAZ
Abstract Anaplastic thyroid cancer (ATC) is one of the most lethal and aggressive human malignancies, with no effective treatment currently available. The Hippo tumor suppressor pathway is highly conserved in mammals and plays an important role in carcinogenesis. TAZ is one of major key effectors of...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-04-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-04781-1 |
| _version_ | 1819209858584412160 |
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| author | Jianing Tang Yongwen Luo Liang Xiao |
| author_facet | Jianing Tang Yongwen Luo Liang Xiao |
| author_sort | Jianing Tang |
| collection | DOAJ |
| description | Abstract Anaplastic thyroid cancer (ATC) is one of the most lethal and aggressive human malignancies, with no effective treatment currently available. The Hippo tumor suppressor pathway is highly conserved in mammals and plays an important role in carcinogenesis. TAZ is one of major key effectors of the Hippo pathway. However, the mechanism supporting abnormal TAZ expression in ATC remains to be characterized. In the present study, we identified USP26, a DUB enzyme in the ubiquitin-specific proteases family, as a bona fide deubiquitylase of TAZ in ATC. USP26 was shown to interact with, deubiquitylate, and stabilize TAZ in a deubiquitylation activity-dependent manner. USP26 depletion significantly decreased ATC cell proliferation, migration, and invasion. The effects induced by USP26 depletion could be rescued by further TAZ overexpression. Depletion of USP26 decreased the TAZ protein level and the expression of TAZ/TEAD target genes in ATC, including CTGF, ANKRD1, and CYR61. In general, our findings establish a previously undocumented catalytic role for USP26 as a deubiquitinating enzyme of TAZ and provides a possible target for the therapy of ATC. |
| first_indexed | 2024-12-23T06:01:58Z |
| format | Article |
| id | doaj.art-a03e67bd34ea4be9ac1d0e6d8c150364 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-12-23T06:01:58Z |
| publishDate | 2022-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-a03e67bd34ea4be9ac1d0e6d8c1503642022-12-21T17:57:40ZengNature Publishing GroupCell Death and Disease2041-48892022-04-011341910.1038/s41419-022-04781-1USP26 promotes anaplastic thyroid cancer progression by stabilizing TAZJianing Tang0Yongwen Luo1Liang Xiao2Department of Liver Surgery, Xiangya Hospital, Clinical Research Center for Breast Cancer Control and Prevention in Hunan Province, Central South UniversityDepartment of Urology, Zhongnan Hospital of Wuhan UniversityDepartment of Liver Surgery, Xiangya Hospital, Clinical Research Center for Breast Cancer Control and Prevention in Hunan Province, Central South UniversityAbstract Anaplastic thyroid cancer (ATC) is one of the most lethal and aggressive human malignancies, with no effective treatment currently available. The Hippo tumor suppressor pathway is highly conserved in mammals and plays an important role in carcinogenesis. TAZ is one of major key effectors of the Hippo pathway. However, the mechanism supporting abnormal TAZ expression in ATC remains to be characterized. In the present study, we identified USP26, a DUB enzyme in the ubiquitin-specific proteases family, as a bona fide deubiquitylase of TAZ in ATC. USP26 was shown to interact with, deubiquitylate, and stabilize TAZ in a deubiquitylation activity-dependent manner. USP26 depletion significantly decreased ATC cell proliferation, migration, and invasion. The effects induced by USP26 depletion could be rescued by further TAZ overexpression. Depletion of USP26 decreased the TAZ protein level and the expression of TAZ/TEAD target genes in ATC, including CTGF, ANKRD1, and CYR61. In general, our findings establish a previously undocumented catalytic role for USP26 as a deubiquitinating enzyme of TAZ and provides a possible target for the therapy of ATC.https://doi.org/10.1038/s41419-022-04781-1 |
| spellingShingle | Jianing Tang Yongwen Luo Liang Xiao USP26 promotes anaplastic thyroid cancer progression by stabilizing TAZ Cell Death and Disease |
| title | USP26 promotes anaplastic thyroid cancer progression by stabilizing TAZ |
| title_full | USP26 promotes anaplastic thyroid cancer progression by stabilizing TAZ |
| title_fullStr | USP26 promotes anaplastic thyroid cancer progression by stabilizing TAZ |
| title_full_unstemmed | USP26 promotes anaplastic thyroid cancer progression by stabilizing TAZ |
| title_short | USP26 promotes anaplastic thyroid cancer progression by stabilizing TAZ |
| title_sort | usp26 promotes anaplastic thyroid cancer progression by stabilizing taz |
| url | https://doi.org/10.1038/s41419-022-04781-1 |
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