IKIP downregulates THBS1/FAK signaling to suppress migration and invasion by glioblastoma cells.

IF 2 4区 医学 Q3 ONCOLOGY Oncology Research Pub Date : 2024-06-20 eCollection Date: 2024-01-01 DOI:10.32604/or.2024.042456
Zhaoying Zhu, Yanjia Hu, Feng Ye, Haibo Teng, Guoliang You, Yunhui Zeng, Meng Tian, Jianguo Xu, Jin Li, Zhiyong Liu, Hao Liu, Niandong Zheng
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Abstract

Background: Inhibitor of NF-κB kinase-interacting protein (IKIP) is known to promote proliferation of glioblastoma (GBM) cells, but how it affects migration and invasion by those cells is unclear.

Methods: We compared levels of IKIP between glioma tissues and normal brain tissue in clinical samples and public databases. We examined the effects of IKIP overexpression and knockdown on the migration and invasion of GBM using transwell and wound healing assays, and we compared the transcriptomes under these different conditions to identify the molecular mechanisms involved.

Results: Based on data from our clinical samples and from public databases, IKIP was overexpressed in GBM tumors, and its expression level correlated inversely with survival. IKIP overexpression in GBM cells inhibited migration and invasion in transwell and wound healing assays, whereas IKIP knockdown exerted the opposite effects. IKIP overexpression in GBM cells that were injected into mouse brain promoted tumor growth but inhibited tumor invasion of surrounding tissue. The effects of IKIP were associated with downregulation of THBS1 mRNA and concomitant inhibition of THBS1/FAK signaling.

Conclusions: IKIP inhibits THBS1/FAK signaling to suppress migration and invasion of GBM cells.

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IKIP 可下调 THBS1/FAK 信号,从而抑制胶质母细胞瘤细胞的迁移和侵袭。
背景:已知NF-κB激酶相互作用蛋白抑制剂(IKIP)可促进胶质母细胞瘤(GBM)细胞的增殖,但它如何影响这些细胞的迁移和侵袭尚不清楚:我们比较了临床样本和公共数据库中胶质瘤组织和正常脑组织的 IKIP 水平。方法:我们比较了临床样本和公共数据库中神经胶质瘤组织和正常脑组织中 IKIP 的水平,并使用跨孔试验和伤口愈合试验研究了 IKIP 过表达和敲除对神经胶质瘤迁移和侵袭的影响,还比较了不同条件下的转录组,以确定其中的分子机制:结果:根据我们的临床样本和公共数据库的数据,IKIP在GBM肿瘤中过表达,其表达水平与生存率成反比。IKIP在GBM细胞中的过表达抑制了跨孔和伤口愈合实验中的迁移和侵袭,而IKIP的敲除则产生了相反的效果。在注射到小鼠脑部的 GBM 细胞中过表达 IKIP 会促进肿瘤生长,但会抑制肿瘤对周围组织的侵袭。IKIP的作用与THBS1 mRNA的下调以及THBS1/FAK信号传导的抑制有关:结论:IKIP可抑制THBS1/FAK信号转导,从而抑制GBM细胞的迁移和侵袭。
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来源期刊
Oncology Research
Oncology Research 医学-肿瘤学
CiteScore
4.40
自引率
0.00%
发文量
56
审稿时长
3 months
期刊介绍: Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.
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