Ubiquitin-specific protease 14 targets PFKL-mediated glycolysis to promote the proliferation and migration of oral squamous cell carcinoma

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...

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Bibliographic Details
Published in:Journal of translational medicine 2024-02, Vol.22 (1), p.193-18, Article 193
Main Authors: Zhang, Xingming, Geng, Lou, Tang, Yi, Wang, Yingying, Zhang, Youping, Zhu, Chujiao, Lei, Hu, Xu, Hanzhang, Zhu, Qi, Wu, Yingli, Gu, Wenli
Format: Article
Language:English
Subjects:
Analysis
Antibodies
Biotechnology
Cancer therapies
Carcinoma, Squamous Cell
Care and treatment
Cell Line, Tumor
Cell migration
Cell Proliferation
Cellulose acetate
Deubiquitination
Diagnosis
Enzymes
Glucose
Glucose metabolism
Glycolysis
Head and Neck Neoplasms
Health aspects
Hospitals
Humans
Liver
Medical prognosis
Metabolism
Metastases
Mouth cancer
Mouth Neoplasms - genetics
Oral cancer
Oral carcinoma
Oral squamous cell carcinoma
OSCC
PFKL
Phosphofructokinase
Phosphofructokinase-1
Plasmids
Squamous cell carcinoma
Squamous Cell Carcinoma of Head and Neck
Tumorigenesis
Tumors
Ubiquitin Thiolesterase
Ubiquitin-proteasome system
Ubiquitin-Specific Proteases
Ubiquitin-specific proteinase
USP14
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Description
Summary: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.
ISSN:1479-5876
1479-5876
DOI:10.1186/s12967-024-04943-z