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G2 and S phase-expressed-1 acts as a putative tumor promoter in cervical cancer by enhancing Wnt/β-catenin signaling via modulation of GSK-3β
Environmental Toxicology ( IF 4.4 ) Pub Date : 2021-05-11 , DOI: 10.1002/tox.23158
Wenting Guo 1 , Jing Zhu 2 , Yuan Zhu 3 , Kai Wang 4, 5
Affiliation  

G2 and S phase-expressed-1 (GTSE1) is currently identified as a key regulator of carcinogenesis. However, the involvement of GTSE1 in cervical cancer is unclear. The aims of this work were to explore the relationship between GTSE1 and cervical cancer. Our data elucidated high GTSE1 expression in cervical cancer tissue, which predicted a poor prognosis in cervical cancer patients. GTSE1 knockdown had tumor-suppressive effects in cervical cancer cells by inhibiting cell proliferative and invasive abilities. GTSE1 knockdown decreased the level of phosphorylated glycogen synthase kinase-3β (GSK-3β) and active β-catenin, resulted in inactivation of Wnt/β-catenin signaling. Suppression of GSK-3β remarkably abolished the GTSE1-knockdown-induced inhibitory effects on Wnt/β-catenin signaling. Suppression of Wnt/β-catenin signaling abolished the GTSE1-overexpression-induced oncogenic effects. Notably, GTSE1 knockdown impeded the in vivo tumorigenicity of cervical cancer cells. In short, this work demonstrates that GTSE1 is overexpressed in cervical cancer and GTSE1 suppression exerts a tumor-inhibiting role in cervical cancer by down-regulating Wnt/β-catenin signaling. Our work underlines a crucial relevance between GTSE1 and cervical cancer progression and suggests GTSE1 as a promising therapeutic target for cervical cancer.

中文翻译:

G2 和 S phase-expressed-1 通过调节 GSK-3β 增强 Wnt/β-catenin 信号传导,在宫颈癌中充当推定的肿瘤启动子

G2 和 S 期表达-1 (GTSE1) 目前被确定为致癌的关键调节因子。然而,GTSE1在宫颈癌中的参与尚不清楚。这项工作的目的是探讨 GTSE1 与宫颈癌之间的关系。我们的数据阐明了宫颈癌组织中的高 GTSE1 表达,这预示着宫颈癌患者的预后不良。GTSE1 敲低通过抑制细胞增殖和侵袭能力在宫颈癌细胞中具有肿瘤抑制作用。GTSE1 敲低降低了磷酸化糖原合酶激酶 3β (GSK-3β) 和活性 β-catenin 的水平,导致 Wnt/β-catenin 信号通路失活。GSK-3β 的抑制显着消除了 GTSE1 敲低诱导的对 Wnt/β-连环蛋白信号传导的抑制作用。Wnt/β-连环蛋白信号的抑制消除了 GTSE1 过表达诱导的致癌作用。值得注意的是,GTSE1 敲低阻碍了宫颈癌细胞的体内致瘤性。简而言之,这项工作表明 GTSE1 在宫颈癌中过度表达,并且 GTSE1 抑制通过下调 Wn​​t/β-catenin 信号传导在宫颈癌中发挥肿瘤抑制作用。我们的工作强调了 GTSE1 与宫颈癌进展之间的重要相关性,并表明 GTSE1 作为宫颈癌的有希望的治疗靶点。
更新日期:2021-07-02
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