The deubiquitinase USP7 stabilizes HER2 expression and promotes breast cancer progression
The overexpression and amplification of HER2 occurs in breast cancer. However, the mechanism of HER2 action in tumor has not yet been elucidated. HER2 can be degraded by the UPS system, and several HER2-associated E3s have been identified, but the DUB for HER2 has not yet been uncovered. Targeted th...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-08-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558625000727 |
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| author | Xiaoyue He Xiaohong Xia Ziying Lei Mengfan Tang Jiangyu Zhang Yuning Liao Hongbiao Huang |
| author_facet | Xiaoyue He Xiaohong Xia Ziying Lei Mengfan Tang Jiangyu Zhang Yuning Liao Hongbiao Huang |
| author_sort | Xiaoyue He |
| collection | DOAJ |
| description | The overexpression and amplification of HER2 occurs in breast cancer. However, the mechanism of HER2 action in tumor has not yet been elucidated. HER2 can be degraded by the UPS system, and several HER2-associated E3s have been identified, but the DUB for HER2 has not yet been uncovered. Targeted therapy against HER2 has achieved impressive efficacy in patients with HER2-positive breast cancer. Herein, using MTS, Western blot, Co-IP, colony formation, RT‒qPCR, EdU, flow cytometry, immunofluorescence assays and xenograft model, we elucidated that USP7 deletion inhibited the growth of HER2-positive breast cancer cell by decreasing HER2 protein abundance. We found that USP7 was highly expressed in HER2-positive breast cancer and the expression of USP7 and HER2 was positively correlated. USP7 overexpression accelerated cell cycle progression. Mechanistically, USP7 interacted with HER2 and decreased HER2 ubiquitination to stabilize its expression. Moreover, USP7 knockdown inhibited tumor growth in vivo and in vitro. In addition, HER2 overexpression partially reversed cell growth inhibition induced by USP7 inhibition. Analyses of clinical samples revealed that USP7 overexpression was associated with poor prognosis in patients with HER2+ breast cancer. Thus, this study revealed that USP7, as a DUB of HER2, may be a potential therapeutic target for patient with HER2+ breast cancer. |
| format | Article |
| id | doaj-art-0b1293e8a5f34a0bb2e7b94d7d231f7b |
| institution | Kabale University |
| issn | 1476-5586 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj-art-0b1293e8a5f34a0bb2e7b94d7d231f7b2025-08-20T03:30:43ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862025-08-016610119210.1016/j.neo.2025.101192The deubiquitinase USP7 stabilizes HER2 expression and promotes breast cancer progressionXiaoyue He0Xiaohong Xia1Ziying Lei2Mengfan Tang3Jiangyu Zhang4Yuning Liao5Hongbiao Huang6Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou 510095, PR China; Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, PR ChinaGuangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou 510095, PR ChinaGuangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou 510095, PR ChinaGuangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou 510095, PR China; Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, PR ChinaGuangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou 510095, PR China; Corresponding authors.Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou 510095, PR China; Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, PR China; Corresponding authors.Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou 510095, PR China; Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, PR China; Corresponding authors.The overexpression and amplification of HER2 occurs in breast cancer. However, the mechanism of HER2 action in tumor has not yet been elucidated. HER2 can be degraded by the UPS system, and several HER2-associated E3s have been identified, but the DUB for HER2 has not yet been uncovered. Targeted therapy against HER2 has achieved impressive efficacy in patients with HER2-positive breast cancer. Herein, using MTS, Western blot, Co-IP, colony formation, RT‒qPCR, EdU, flow cytometry, immunofluorescence assays and xenograft model, we elucidated that USP7 deletion inhibited the growth of HER2-positive breast cancer cell by decreasing HER2 protein abundance. We found that USP7 was highly expressed in HER2-positive breast cancer and the expression of USP7 and HER2 was positively correlated. USP7 overexpression accelerated cell cycle progression. Mechanistically, USP7 interacted with HER2 and decreased HER2 ubiquitination to stabilize its expression. Moreover, USP7 knockdown inhibited tumor growth in vivo and in vitro. In addition, HER2 overexpression partially reversed cell growth inhibition induced by USP7 inhibition. Analyses of clinical samples revealed that USP7 overexpression was associated with poor prognosis in patients with HER2+ breast cancer. Thus, this study revealed that USP7, as a DUB of HER2, may be a potential therapeutic target for patient with HER2+ breast cancer.http://www.sciencedirect.com/science/article/pii/S1476558625000727USP7HER2 Positive breast cancerUbiquitinationGrowth |
| spellingShingle | Xiaoyue He Xiaohong Xia Ziying Lei Mengfan Tang Jiangyu Zhang Yuning Liao Hongbiao Huang The deubiquitinase USP7 stabilizes HER2 expression and promotes breast cancer progression Neoplasia: An International Journal for Oncology Research USP7 HER2 Positive breast cancer Ubiquitination Growth |
| title | The deubiquitinase USP7 stabilizes HER2 expression and promotes breast cancer progression |
| title_full | The deubiquitinase USP7 stabilizes HER2 expression and promotes breast cancer progression |
| title_fullStr | The deubiquitinase USP7 stabilizes HER2 expression and promotes breast cancer progression |
| title_full_unstemmed | The deubiquitinase USP7 stabilizes HER2 expression and promotes breast cancer progression |
| title_short | The deubiquitinase USP7 stabilizes HER2 expression and promotes breast cancer progression |
| title_sort | deubiquitinase usp7 stabilizes her2 expression and promotes breast cancer progression |
| topic | USP7 HER2 Positive breast cancer Ubiquitination Growth |
| url | http://www.sciencedirect.com/science/article/pii/S1476558625000727 |
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