<p>USP13 serves as a tumor suppressor via the PTEN/AKT pathway in oral squamous cell carcinoma</p>

Abstract

Background: Recent studies have shown that USP13 a deubiquitinase, serves as an important regulator of tumorigenesis. However, the biological role of USP13 in oral squamous cell carcinoma (OSCC) remains enigmatic.Materials and methods: We examined USP13 expression in OSCC and adjacent normal tissues by immunohistochemical staining. The biological functions of USP13 in OSCC cells and the possible underlying mechanisms were investigated.Results: In this study, we showed that USP13 expression was frequently reduced in human OSCC specimens and that the reduction was correlated with the clinical stage. Functional studies demonstrated that overexpression of USP13 suppressed OSCC cell proliferation, glucose uptake and lactate production in vitro and inhibited tumor growth in vivo. Furthermore, USP13 overexpression induced phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression and repressed the activation of AKT as well as the expression of the downstream effectors glucose transporter-1 (GLUT1) and hexokinase-2 (HK2). Overexpression of PTEN reversed the USP13-knockdown-induced glucose uptake, lactate production, AKT activation, and expression of GLUT1 and HK2.Conclusion: Our findings suggest that USP13 serves as a tumor suppressor by regulating the PTEN/AKT signaling pathway in OSCC cells, improving our understanding of OSCC progression and providing a clue for the development of a novel cancer therapy.

Molecular Mechanisms of DUBs Regulation in Signaling and Disease

“…Therefore, research on deubiquitinating enzymes has always attracted much attention to the pharmaceutical industry. Research in recent decades has shown that deubiquitinating enzymes can regulate multiple signaling pathways [33][34][35][36], suggesting to researchers the development of new medicines based on the pathogenesis of different diseases that can target deubiquitinating enzymes. For example, the development of deubiquitinating enzyme inhibitors [185], especially selective inhibitors, may have a good therapeutic effect [186,187].…”

“…Therefore, disease treatment strategies with DUBs as molecular targets have a broad development value and promising clinical application prospects [32]. Many studies have shown DUBs involvement in the regulation of Wnt/β-catenin signaling, TGF-β (transforming growth factor-β), Akt (Protein Kinase B), NF-κB (nuclear factor kappa-lightchain-enhancer of activated B cells) and other cancer-related pathways [33][34][35][36].…”

Molecular profiling of immune cell-enriched Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) interacting protein USP13

“…The data in the literature regarding the role of USP13 in carcinogenesis is controversial. Some studies propose that USP13 favors tumor progression and plays an oncogenic role in glioma [ 30 ], melanoma [ 31 ], ovarian cancer [ 32 ] and lung cancer [ 33 ] while others claim that it functions as a tumor suppressor in oral squamous cell carcinoma [ 34 ], breast cancer [ 15 ] and bladder cancer [ 35 ]. Collectively, these data suggest a context-dependent role for USP13 in cancer.…”

Role of Deubiquitinases in Human Cancers: Potential Targeted Therapy

“…USP13 also acts as a tumor suppressor through its regulation of the phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/AKT pathway in oral squamous cell carcinoma. Overexpression of USP13 induces PTEN expression and represses the activation of AKT, glucose transporter-1, and hexokinase-2, leading to growth inhibition [84]. In an RNAi screen, USP11 was identified as a promyelocytic leukemia (PML) regulator to deubiquitinate and stabilize PML, counteracting the functions of PML.…”