profilin - 2在肺腺癌中调节丙酮酸激酶M2核易位和促进肿瘤血管生成中的新颖性。

IF 5.8 2区 医学 Q1 Medicine
Xiaohui Du, Chi Ma, Yingyan Wang, Mingxin Xu, Yanbin Kuang, Mengyun Li, Shuang Wen, Peipei He, Hui Zhao, Qi Wang
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引用次数: 0

摘要

背景:PFN2在所有生物体中不可或缺,对癌症的发生和发展至关重要。本研究中,我们发现PFN2在肺腺癌(LUAD)患者预后不良的肿瘤组织中高度过表达,在调节血管生成中具有新的作用。然而,pfn2介导的LUAD血管生成的机制尚不清楚。方法:采用免疫组化和免疫印迹法检测组织或肺癌细胞中相关蛋白的表达水平。为了阐明潜在的机制,我们通过质谱、共免疫沉淀和分子建模技术鉴定了PFN2的结合伙伴。此外,我们利用能够模拟肿瘤缺氧微环境的三维液滴血管生成模型研究了PFN2促进血管生成的功能。结果:我们的发现显示PFN2在肿瘤中与邻近非肿瘤组织相比过表达。其敲低可通过缺氧相关的NF-κB/HIF-1α信号通路显著抑制LUAD细胞的增殖和血管生成,并降低血管内皮生长因子(VEGF)。此外,丙酮酸激酶M2 (PKM2)是糖酵解过程中的关键酶,是PFN2的一个新的结合伙伴。PKM2的核易位依赖于PFN2的表达及其相互作用,从而在肺癌中功能性地调节血管生成。结论:本研究发现癌基因PFN2通过调控PKM2核易位促进LUAD肿瘤血管生成,为LUAD治疗提供了新的分子靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The novelty of profilin 2 in regulating pyruvate kinase M2 nuclear translocation and promoting tumor angiogenesis in lung adenocarcinoma.

Background: Profilin 2 (PFN2), indispensable in all organisms, is important for cancer initiation and progression. Here, we found PFN2 highly overexpressed in tumor tissues with poor prognosis of Lung adenocarcinoma (LUAD) patients had a novel role in remodulating angiogenesis. However, the mechanism of PFN2-mediated LUAD angiogenesis remains unelucided.

Methods: Immunohistochemistry and western blotting were used to detected the expression levels of related proteins in tissue or lung cancer cells. To elucidate the underlying mechanisms, we identified binding partners of PFN2 through mass spectrometry, co-immunoprecipitation, and molecular modeling techniques. Additionally, we investigated the angiogenic-promoting function of PFN2 utilizing a three-dimensional droplet-based angiogenesis model capable of simulating the tumor hypoxic microenvironment.

Results: Our finding reveal that PFN2 was overexpressed in tumors compared with the adjacent nontumor tissues. Its knockdown markedly impaired the proliferation, and angiogenesis of LUAD cells via hypoxia-related NF-κB/HIF-1α signaling pathway, with vascular endothelial growth Factor (VEGF) decrease. Additionally, pyruvate kinase M2 (PKM2), a pivotal enzyme in glycolysis, is a novel binding partner of PFN2. The nuclear translocation of PKM2 was observed to be dependent on PFN2 expression and their interaction, which functionally modulates angiogenesis in lung cancer.

Conclusions: Our study revealed oncogene PFN2 promoted tumor angiogenesis in LUAD through regulating PKM2 nuclear translocation, providing novel molecular therapy targets for LUAD treatment.

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来源期刊
Respiratory Research
Respiratory Research RESPIRATORY SYSTEM-
CiteScore
9.70
自引率
1.70%
发文量
314
审稿时长
4-8 weeks
期刊介绍: Respiratory Research publishes high-quality clinical and basic research, review and commentary articles on all aspects of respiratory medicine and related diseases. As the leading fully open access journal in the field, Respiratory Research provides an essential resource for pulmonologists, allergists, immunologists and other physicians, researchers, healthcare workers and medical students with worldwide dissemination of articles resulting in high visibility and generating international discussion. Topics of specific interest include asthma, chronic obstructive pulmonary disease, cystic fibrosis, genetics, infectious diseases, interstitial lung diseases, lung development, lung tumors, occupational and environmental factors, pulmonary circulation, pulmonary pharmacology and therapeutics, respiratory immunology, respiratory physiology, and sleep-related respiratory problems.
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