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IQUB 的上调通过激活 Akt/GSK3β/β-连环蛋白信号通路促进乳腺癌细胞的增殖和迁移。

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

机构信息

Hubei Provincial Key Laboratory of Developmentally Originated Disease, Department of Pathology and Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, China.

Department of Anatomy, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, China.

出版信息

Cancer Med. 2018 Aug;7(8):3875-3888. doi: 10.1002/cam4.1568. Epub 2018 Jul 2.

Abstract

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.

摘要

乳腺癌是女性肿瘤发病率最高的一种,严重威胁着女性的健康。我们之前的研究通过转录组测序发现 IQUB(含 IQ 基序和泛素结构域)在乳腺癌的发展过程中表达显著增加。然而,目前还没有关于 IQUB 在肿瘤发生中的作用机制的研究。进一步的研究表明,IQUB 在乳腺癌中的表达显著增加,通过组织微阵列分析发现,其与乳腺癌的病理分化具有显著的正相关性。此外,我们还发现 IQUB 过表达可以明显促进 MCF-7 细胞的增殖和迁移,并增加 MCF-7 细胞在体外研究中 S 和 G2/M 期的比例,而 IQUB 的敲低则导致 MDA-MB-231 细胞增殖和迁移的抑制,并增加 MDA-MB-231 细胞在 G1 期的比例。此外,IQUB 的过表达或敲低与 Licl 或 MG-132 的联合处理表明,IQUB 通过激活 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,这些结果表明,上调的 IQUB 通过激活 Akt/GSK3β/β-catenin 信号通路促进乳腺癌细胞的增殖和迁移,在乳腺癌的发生和发展中发挥着重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1064/6089180/23fe60dff355/CAM4-7-3875-g001.jpg

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