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S期激酶相关蛋白2促进骨肉瘤细胞的生长和迁移。

S-phase kinase-associated protein 2 promotes cell growth and motility in osteosarcoma cells.

作者信息

Ding Lu, Li Rong, Sun Rongxin, Zhou Yang, Zhou Yubo, Han Xiaoping, Cui Yong, Wang Wu, Lv Qing, Bai Jingping

机构信息

a Department of Orthopedics , Fifth Affiliated Hospital, Xinjiang Medical University , Xinjiang , China.

b Department of Orthopedics , Tumor Hospital Affiliated to Xinjiang Medical University , Xinjiang , China.

出版信息

Cell Cycle. 2017 Aug 18;16(16):1547-1555. doi: 10.1080/15384101.2017.1346760. Epub 2017 Aug 3.

DOI:10.1080/15384101.2017.1346760
PMID:28771075
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5584850/
Abstract

Skp2 (S-phase kinase-associated protein 2) plays an oncogenic role in a variety of human cancers. However, the function of Skp2 in osteosarcoma (OS) is elusive. Therefore, in the current study, we explore whether Skp2 exerts its oncogenic function in OS. The cell growth, apoptosis, invasion and cell cycle were measured in OS cells after Skp2 overexpression. We found that overexpression of Skp2 enhanced cell growth, and inhibited cell apoptosis in OS cells. Moreover, we observed that upregulation of Skp2 accelerated cell cycle progression in OS cells. Furthermore, the ability of migration and invasion was enhanced in Skp2 overexpressing OS cells. Mechanically, our Western blotting data suggested that Skp2 decreased the expression of E-cadherin, Foxo1, p21, and p57, but increased MMP-9 in OS cells. In conclusion, our study demonstrated that Skp2 exhibited an oncogenic function in OS cells, suggesting that inhibition of Skp2 may be a novel approach for the treatment of OS.

摘要

Skp2(S期激酶相关蛋白2)在多种人类癌症中发挥致癌作用。然而,Skp2在骨肉瘤(OS)中的功能尚不清楚。因此,在本研究中,我们探讨Skp2是否在OS中发挥其致癌功能。在Skp2过表达后,检测OS细胞中的细胞生长、凋亡、侵袭和细胞周期。我们发现Skp2的过表达增强了OS细胞的生长,并抑制了细胞凋亡。此外,我们观察到Skp2的上调加速了OS细胞的细胞周期进程。此外,Skp2过表达的OS细胞迁移和侵袭能力增强。机制上,我们的蛋白质印迹数据表明,Skp2降低了OS细胞中E-钙黏蛋白、Foxo1、p21和p57的表达,但增加了MMP-9的表达。总之,我们的研究表明Skp2在OS细胞中表现出致癌功能,提示抑制Skp2可能是治疗OS的一种新方法。

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本文引用的文献

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Phosphorylation by mTORC1 stablizes Skp2 and regulates its oncogenic function in gastric cancer.mTORC1介导的磷酸化作用可稳定Skp2,并调控其在胃癌中的致癌功能。
Mol Cancer. 2017 Apr 26;16(1):83. doi: 10.1186/s12943-017-0649-0.
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Germline and somatic genetics of osteosarcoma - connecting aetiology, biology and therapy.成骨肉瘤的胚系和体细胞遗传学:连接病因学、生物学和治疗学。
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Exploring targeted therapy of osteosarcoma using proteomics data.利用蛋白质组学数据探索骨肉瘤的靶向治疗
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The β-TrCP-FBXW2-SKP2 axis regulates lung cancer cell growth with FBXW2 acting as a tumour suppressor.β-TrCP-FBXW2-SKP2 轴通过 FBXW2 作为肿瘤抑制因子调节肺癌细胞生长。
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Cancer Statistics, 2017.《2017 年癌症统计》
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Matrine derivative YF-18 inhibits lung cancer cell proliferation and migration through down-regulating Skp2.苦参碱衍生物YF-18通过下调Skp2抑制肺癌细胞的增殖和迁移。
Oncotarget. 2017 Feb 14;8(7):11729-11738. doi: 10.18632/oncotarget.14329.
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Oncogene. 2017 Mar;36(10):1364-1373. doi: 10.1038/onc.2016.300. Epub 2016 Nov 21.
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Am J Cancer Res. 2016 Oct 1;6(10):2178-2191. eCollection 2016.
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Rottlerin exerts its anti-tumor activity through inhibition of Skp2 in breast cancer cells.罗特勒素通过抑制乳腺癌细胞中的Skp2发挥其抗肿瘤活性。
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Increased expression of SKP2 is an independent predictor of locoregional recurrence in cervical cancer via promoting DNA-damage response after irradiation.SKP2表达增加是宫颈癌局部区域复发的独立预测因子,其通过促进放疗后的DNA损伤反应来实现。
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