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整合素连接激酶(ILK)的过表达通过 NF-κB 通路促进神经胶质瘤细胞的侵袭和迁移,并下调 E-钙黏蛋白。

Overexpression of integrin-linked kinase (ILK) promotes glioma cell invasion and migration and down-regulates E-cadherin via the NF-κB pathway.

机构信息

Department of Neurosurgery, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, Liaoning, People's Republic of China.

出版信息

J Mol Histol. 2014 Apr;45(2):141-51. doi: 10.1007/s10735-013-9540-5. Epub 2013 Sep 13.

DOI:10.1007/s10735-013-9540-5
PMID:24045896
Abstract

Integrin-linked kinase (ILK) is a ubiquitously expressed serine/threonine protein kinase that has been implicated in cancer development, progression and metastasis. The aim of the present study was to characterize the role of ILK in glioma cell invasion and migration. We generated a recombinant eukaryotic expression vector containing the human ILK gene and transfected it into human glioma SHG-44 cells. Real-time PCR and western blot analysis were used to identify the stable transformants. The wound healing and Transwell invasion assays showed that ectopic overexpression of ILK in SHG-44 cells significantly promoted their migration and invasion capabilities in culture. This was accompanied by a decrease in expression of E-cadherin and an increase in expression of Snail and Slug. Moreover, the decrease in E-cadherin expression induced by ILK overexpression was greatly restored by the nuclear factor-κB (NF-κB) inhibitor BAY 11-7028 or small interfering RNA targeting NF-κB p65, indicating an involvement of NF-κB in ILK-induced down-regulation of E-cadherin. In conclusion, our data underscore a novel role for ILK in glioma invasion and metastasis processes, implicating potential for therapeutic interference.

摘要

整合素连接激酶(ILK)是一种普遍表达的丝氨酸/苏氨酸蛋白激酶,已被牵涉到癌症的发生、发展和转移中。本研究旨在探讨 ILK 在神经胶质瘤细胞侵袭和迁移中的作用。我们构建了一个包含人 ILK 基因的重组真核表达载体,并将其转染入人神经胶质瘤 SHG-44 细胞中。实时 PCR 和 Western blot 分析用于鉴定稳定转染的细胞。划痕愈合和 Transwell 侵袭实验表明,ILK 在 SHG-44 细胞中的异位过表达显著促进了它们在培养中的迁移和侵袭能力。这伴随着 E-钙黏蛋白表达的降低和 Snail 和 Slug 表达的增加。此外,ILK 过表达诱导的 E-钙黏蛋白表达降低,通过核因子-κB(NF-κB)抑制剂 BAY 11-7028 或靶向 NF-κB p65 的小干扰 RNA 得到了极大的恢复,表明 NF-κB 参与了 ILK 诱导的 E-钙黏蛋白下调。总之,我们的数据强调了 ILK 在神经胶质瘤侵袭和转移过程中的新作用,暗示了治疗干预的潜力。

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2
Small interfering RNA targeting ILK inhibits metastasis in human tongue cancer cells through repression of epithelial-to-mesenchymal transition.靶向整合素连接激酶的小干扰 RNA 通过抑制上皮-间充质转化抑制人舌癌细胞的转移。
Exp Cell Res. 2013 Aug 1;319(13):2058-2072. doi: 10.1016/j.yexcr.2013.05.014. Epub 2013 May 23.
3
LASS2主要通过抑制上皮-间质转化(EMT)和促进细胞凋亡来损害胶质瘤干细胞的增殖以及胶质瘤细胞的迁移和侵袭。
J Cancer. 2022 Apr 18;13(7):2281-2292. doi: 10.7150/jca.71256. eCollection 2022.
4
Emodin Reverses the Epithelial-Mesenchymal Transition of Human Endometrial Stromal Cells by Inhibiting ILK/GSK-3β Pathway.大黄素通过抑制 ILK/GSK-3β 通路逆转人子宫内膜间质细胞的上皮间质转化。
Drug Des Devel Ther. 2020 Sep 10;14:3663-3672. doi: 10.2147/DDDT.S262816. eCollection 2020.
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Significance of integrin-linked kinase (ILK) in tumorigenesis and its potential implication as a biomarker and therapeutic target for human cancer.整合素连接激酶(ILK)在肿瘤发生中的意义及其作为人类癌症生物标志物和治疗靶点的潜在意义。
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