Ubiquitin-specific protease 14 targets PFKL-mediated glycolysis to promote the proliferation and migration of oral squamous cell carcinoma
Abstract Aberrant upregulation of the ubiquitin-specific protease 14 (USP14) has been found in some malignant tumors, including oral squamous cell carcinoma (OSCC). In this study, we further demonstrated that aberrantly overexpressed USP14 was also closely related to adverse clinicopathological feat...
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-024-04943-z |
| _version_ | 1797273470691704832 |
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| author | Xingming Zhang Lou Geng Yi Tang Yingying Wang Youping Zhang Chujiao Zhu Hu Lei Hanzhang Xu Qi Zhu Yingli Wu Wenli Gu |
| author_facet | Xingming Zhang Lou Geng Yi Tang Yingying Wang Youping Zhang Chujiao Zhu Hu Lei Hanzhang Xu Qi Zhu Yingli Wu Wenli Gu |
| author_sort | Xingming Zhang |
| collection | DOAJ |
| description | Abstract Aberrant upregulation of the ubiquitin-specific protease 14 (USP14) has been found in some malignant tumors, including oral squamous cell carcinoma (OSCC). In this study, we further demonstrated that aberrantly overexpressed USP14 was also closely related to adverse clinicopathological features and poor prognosis in patients with OSCC, so we hypothesized that USP14 might act as a tumor-promoting factor during the progression of OSCC. Notably, we originally proved that USP14 is a deubiquitinating enzyme for phosphofructokinase-1 liver type (PFKL), a key rate-limiting enzyme involved in the glycolytic pathway. USP14 interacts with PFKL and enhances its stability through deubiquitination in OSCC cells, which in turn enhances PFKL-mediated glycolytic metabolism and ultimately promote cellular proliferation, migration, and tumorigenesis. In this work, we have also demonstrated for the first time that USP14 is a critical regulator of glycolysis in OSCC and verified a novel mechanism whereby it is involved in tumor metastasis and growth. Collectively, our findings provide novel insights into the tumor-promoting role of USP14 and establish mechanistic foundations for USP14-targeting therapies. |
| first_indexed | 2024-03-07T14:43:44Z |
| format | Article |
| id | doaj.art-7b27daded76546458e3365984e7fa120 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-07T14:43:44Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-7b27daded76546458e3365984e7fa1202024-03-05T20:06:22ZengBMCJournal of Translational Medicine1479-58762024-02-0122111810.1186/s12967-024-04943-zUbiquitin-specific protease 14 targets PFKL-mediated glycolysis to promote the proliferation and migration of oral squamous cell carcinomaXingming Zhang0Lou Geng1Yi Tang2Yingying Wang3Youping Zhang4Chujiao Zhu5Hu Lei6Hanzhang Xu7Qi Zhu8Yingli Wu9Wenli Gu10Department of Clinical Laboratory, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Clinical Laboratory, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Clinical Laboratory, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineHongqiao International Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of MedicineHongqiao International Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of MedicineHongqiao International Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of MedicineHongqiao International Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of MedicineHongqiao International Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of MedicineDepartment of Hematology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineHongqiao International Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of MedicineDepartment of Clinical Laboratory, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineAbstract Aberrant upregulation of the ubiquitin-specific protease 14 (USP14) has been found in some malignant tumors, including oral squamous cell carcinoma (OSCC). In this study, we further demonstrated that aberrantly overexpressed USP14 was also closely related to adverse clinicopathological features and poor prognosis in patients with OSCC, so we hypothesized that USP14 might act as a tumor-promoting factor during the progression of OSCC. Notably, we originally proved that USP14 is a deubiquitinating enzyme for phosphofructokinase-1 liver type (PFKL), a key rate-limiting enzyme involved in the glycolytic pathway. USP14 interacts with PFKL and enhances its stability through deubiquitination in OSCC cells, which in turn enhances PFKL-mediated glycolytic metabolism and ultimately promote cellular proliferation, migration, and tumorigenesis. In this work, we have also demonstrated for the first time that USP14 is a critical regulator of glycolysis in OSCC and verified a novel mechanism whereby it is involved in tumor metastasis and growth. Collectively, our findings provide novel insights into the tumor-promoting role of USP14 and establish mechanistic foundations for USP14-targeting therapies.https://doi.org/10.1186/s12967-024-04943-zUSP14DeubiquitinationPFKLGlycolysisOSCC |
| spellingShingle | Xingming Zhang Lou Geng Yi Tang Yingying Wang Youping Zhang Chujiao Zhu Hu Lei Hanzhang Xu Qi Zhu Yingli Wu Wenli Gu Ubiquitin-specific protease 14 targets PFKL-mediated glycolysis to promote the proliferation and migration of oral squamous cell carcinoma Journal of Translational Medicine USP14 Deubiquitination PFKL Glycolysis OSCC |
| title | Ubiquitin-specific protease 14 targets PFKL-mediated glycolysis to promote the proliferation and migration of oral squamous cell carcinoma |
| title_full | Ubiquitin-specific protease 14 targets PFKL-mediated glycolysis to promote the proliferation and migration of oral squamous cell carcinoma |
| title_fullStr | Ubiquitin-specific protease 14 targets PFKL-mediated glycolysis to promote the proliferation and migration of oral squamous cell carcinoma |
| title_full_unstemmed | Ubiquitin-specific protease 14 targets PFKL-mediated glycolysis to promote the proliferation and migration of oral squamous cell carcinoma |
| title_short | Ubiquitin-specific protease 14 targets PFKL-mediated glycolysis to promote the proliferation and migration of oral squamous cell carcinoma |
| title_sort | ubiquitin specific protease 14 targets pfkl mediated glycolysis to promote the proliferation and migration of oral squamous cell carcinoma |
| topic | USP14 Deubiquitination PFKL Glycolysis OSCC |
| url | https://doi.org/10.1186/s12967-024-04943-z |
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