Overexpression of the human ZNF300 gene enhances growth and metastasis of cancer cells through activating NF-kB pathway.

Overexpression of the human ZNF300 gene enhances growth and metastasis of cancer cells through activating NF-kB pathway.
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DOI:
10.1111/j.1582-4934.2011.01388.x
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发表时间:
2012-05
影响因子:
5.3
通讯作者:
Li WX
Li WX
中科院分区:
医学2区
文献类型:
--
作者:
Wang T;Wang XG;Xu JH;Wu XP;Qiu HL;Yi H;Li WX

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锌指蛋白在多种生理过程中发挥重要作用。在这里,我们报告了ZNF 300,一种新的锌指蛋白,在人类中特异性地鉴定,通过调节NF-κB通路促进肿瘤的发展。炎症因子可诱导HeLa细胞表达ZNF 300,ZNF 300的表达通过激活TRAF 2和与IKKβ相互作用进一步增强NF-κB信号转导。ZNF 300过表达可增加ERK 1/2磷酸化水平和c-myc、IL-6、IL-8的表达,但降低p21 waf-1和p27 Kip 1的表达,而下调p21 waf-1和p27 Kip 1的表达则产生相反的作用。最重要的是,ZNF 300的过表达在体外刺激癌细胞增殖,并显著增强小鼠异种移植模型中肿瘤的发展和转移,而敲低ZNF 300导致相反的效果。我们已经确定了ZNF 300在肿瘤发展中的一种新功能,该功能可能是人类而非小鼠中炎症和NF-κB与肿瘤发生的唯一联系。
Zinc finger proteins (ZNF) play important roles in various physiological processes. Here we report that ZNF300, a novel zinc finger protein, identified specifically in humans, promotes tumour development by modulating the NF-κB pathway. Inflammatory factors were found to induce ZNF300 expression in HeLa cell line, and ZNF300 expression further enhanced NF-κB signalling by activating TRAF2 and physically interacting with IKKβ. Furthermore, ZNF300 overexpression increased ERK1/2 phosphorylation and the expression of c-myc, IL-6, and IL-8 but decreased the expression of p21waf-1 and p27Kip1; whose down-regulation led to the opposite effect. Most importantly, ZNF300 overexpression stimulated cancer cell proliferation in vitro and significantly enhanced tumour development and metastasis in mouse xenograft model, while knocking down ZNF300 led to the opposite effects. We have identified a novel function for ZNF300 in tumour development that may uniquely link inflammation and NF-κB to tumourigenesis in humans but not in mice.
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