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
Abstract
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.
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.