CEP55 Promotes Cell Motility via JAK2⁻STAT3⁻MMPs Cascade in Hepatocellular Carcinoma.

CEP55 Promotes Cell Motility via JAK2⁻STAT3⁻MMPs Cascade in Hepatocellular Carcinoma.
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CEP55 通过 JAK2(-)STAT3(-)MMP 级联促进肝细胞癌中的细胞运动

DOI:
10.3390/cells7080099
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发表时间:
2018-08-08
期刊:
影响因子:
6
通讯作者:
Yin Y
Yin Y
中科院分区:
生物学2区
文献类型:
--
作者:
Li M;Gao J;Li D;Yin Y

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肝细胞癌(Hepatocellular carcinoma,HCC)是最常见的恶性肿瘤之一,预后差。因此,迫切需要新的诊断或预后生物标志物和潜在的治疗靶点。CEP 55在调节物理胞质分裂中起着至关重要的作用。CEP 55是否以及如何促进HCC的发展尚不清楚。在此,我们证明CEP 55在HCC组织中异常上调,并且这些高水平的CEP 55与HCC患者的不良预后密切相关。CEP 55表达的敲低显著抑制HCC细胞的迁移和侵袭。我们还证明了CEP 55在生理上与JAK 2相互作用并促进其磷酸化;因此,它是JAK 2-STAT 3信号转导及其靶基因MMP 2/9的新型调节剂。最后,阻断JAK 2或STAT 3减弱了由于CEP 55过表达引起的迁移和侵袭的刺激。综上所述,我们的研究结果表明,CEP 55作为一种癌基因,通过调节JAK 2-STAT 3-MMPs信号通路促进HCC细胞的迁移和侵袭。
Hepatocellular carcinoma (HCC) is one of the most common malignancies and has a poor prognosis. Novel diagnostic or prognostic biomarkers and potential therapeutic targets for HCC are thus urgently needed. CEP55 plays a crucial role in regulating physical cytokinesis. Whether, and how, CEP55 contributes to HCC development remains unclear. Herein, we demonstrate that CEP55 is abnormally upregulated in HCC tissue, and these high levels of CEP55 are closely related to the poor prognosis of HCC patients. Knockdown of CEP55 expression significantly inhibits HCC cell migration and invasion. We also demonstrate that CEP55 physiologically interacts with JAK2 and promotes its phosphorylation; thus, it is a novel regulator of JAK2–STAT3 signaling and its target genes MMP2/9. Finally, blocking JAK2 or STAT3 blunts the stimulation of migration and invasion due to CEP55 overexpression. In summary, our results suggest that CEP55, as an oncogene, promotes HCC cell migration and invasion through regulating JAK2–STAT3–MMPs signaling.
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