Upregulated IQUB promotes cell proliferation and migration via activating Akt/GSK3β/β-catenin signaling pathway in breast cancer.

Upregulated IQUB promotes cell proliferation and migration via activating Akt/GSK3β/β-catenin signaling pathway in breast cancer.
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DOI:
10.1002/cam4.1568
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发表时间:
2018-08
期刊:
影响因子:
4
通讯作者:
Wei L
Wei L
中科院分区:
医学3区
文献类型:
--
作者:
Li K;Ma YB;Zhang Z;Tian YH;Xu XL;He YQ;Xu L;Gao Y;Pan WT;Song WJ;He X;Wei L

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乳腺癌是女性发病率最高的肿瘤,严重威胁着女性的健康。我们前期的研究通过转录组测序发现,IQUB(含有IQ基序和泛素结构域)的表达在乳腺癌的发生过程中显着增加。但目前尚无关于IQUB在肿瘤发生中的作用机制的研究。进一步研究显示,组织芯片分析表明,IQUB在乳腺癌中表达显着升高,与乳腺癌的病理分化程度呈显着正相关。此外,体外研究还发现IQUB过表达可明显促进MCF-7细胞的增殖和迁移,增加MCF-7细胞S期和G2/M期的比例,而敲低IQUB则抑制MDA-MB-231细胞的增殖和迁移,增加MDA-MB-231细胞G1期的比例。此外,IQUB过表达或敲低结合Licl或MG-132治疗表明,IQUB激活Akt促进GSK3β磷酸化,进而激活乳腺癌细胞中的Wnt/β-catenin信号通路。综上所述,上调的IQUB通过激活Akt/GSK3β/β-catenin信号通路促进乳腺癌细胞增殖和迁移,在乳腺癌的发生和发展中发挥重要作用。
Breast cancer was the highest incidence of tumor in women, which seriously threaten women's health. Our previous study found that the expression of IQUB (IQ motif and ubiquitin domain containing) was significantly increased in the development of breast cancer by transcriptome sequencing. However, there were no studies on the mechanism of IQUB in tumorigenesis. Further study showed that IQUB expression was significantly increased in breast cancer, which had a significantly positive correlation with pathological differentiation of breast cancer by tissue microarray analysis. Furthermore, we also discovered that IQUB overexpression could obviously promote the proliferation and migration of MCF‐7 cells and increase the proportion of MCF‐7 cells in S and G2/M phase in vitro study, while knockdown of IQUB caused inhibition of cell proliferation and migration in MDA‐MB‐231 cells and increased the proportion of MDA‐MB‐231 cells in G1 phase. Furthermore, IQUB overexpression or knockdown combined with treatment of Licl or MG‐132 showed that IQUB activated Akt to promote GSK3β phosphorylation, which in turn activated Wnt/β‐catenin signaling pathway in breast cancer cells. Taken together, these results indicated that upregulated IQUB promoted breast cancer cell proliferation and migration via activating Akt/GSK3β/β‐catenin signaling pathway, which played an important part in the tumorigenesis and development of breast cancer.
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