USP13 serves as a tumor suppressor via the PTEN/AKT pathway in oral squamous cell carcinoma
USP13 serves as a tumor suppressor via the PTEN/AKT pathway in oral squamous cell carcinoma
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DOI：
10.2147/cmar.s186829
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发表时间：
2019-01-01
影响因子：
3.3
通讯作者：
Liu, Weixian
中科院分区：
文献类型：
--
作者：
Qu, Zhi;Zhang, Ran;Liu, Weixian
背景：最近的研究表明，USP13是一种脱泛素酶，是肿瘤发生的重要调节因子。然而，USP13在口腔鳞状细胞癌(OSCC)中的生物学作用仍是个谜。材料与方法：采用免疫组织化学方法检测USP13在口腔鳞状细胞癌及癌旁正常组织中的表达。研究了USP13在口腔鳞癌细胞中的生物学功能及其可能的机制。结果：在本研究中，口腔鳞癌组织中USP13的表达水平普遍降低，且这种降低与临床分期有关。功能研究表明，USP13过表达可在体外抑制口腔鳞癌细胞的增殖、葡萄糖摄取和乳酸的产生，并抑制体内肿瘤的生长。此外，USP13过表达诱导了10号染色体缺失的磷酸酶和张力蛋白同源基因(PTEN)的表达，并抑制了AKT的激活以及下游效应因子葡萄糖转运体-1(GLUT1)和己糖激酶-2(HK2)的表达。PTEN过表达逆转了USP13基因敲除诱导的葡萄糖摄取、乳酸生成、AKT激活以及GLUT1和HK2的表达。结论：USP13可能通过调节PTEN/AKT而发挥肿瘤抑制作用。OSCC细胞中的信号通路，提高了我们对OSCC进展的理解，并为开发新的癌症治疗方法提供了线索。
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.