ArticleJournal of experimental & clinical cancer research : CR2019
Mammalian Eps15 homology domain 1 potentiates angiogenesis of non-small cell lung cancer by regulating β2AR signaling.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- A Quarter Century of EHD Protein Research: From Endosomal Recycling to Ciliopathies.Traffic (Copenhagen, Denmark) · 2026Review
- Endocytic Adaptor Proteins in Vascular Diseases: Critical Role of Intracellular Trafficking in Regulating Pathobiology of Vascular Disorders.Cardiology discovery · 2026Review
- Epstein-Barr virus (EBV) infection of endothelial cells via endocytosis is associated with a poor prognosis in nasopharyngeal carcinoma.Microbiology spectrum · 2025Article
- Systematic Analysis to Identify the MIR99AHG-has-miR-21-5p-Journal of Cancer · 2024Article
- EHD1-dependent traffic of IGF-1 receptor to the cell surface is essential for Ewing sarcoma tumorigenesis and metastasis.Communications biology · 2023Article
- A novel EHD1/CD44/Hippo/SP1 positive feedback loop potentiates stemness and metastasis in lung adenocarcinoma.Clinical and translational medicine · 2022Article
- lncRNA EPS15-AS1 affects the biological behavior of liver cancer stem cells by regulating EPS15 expression.American journal of translational research · 2022Article
- Expression of ADRB2 in children with neuroblastoma and its influence on prognosis.Frontiers in surgery · 2022Article
- Article
- The role of ADRB2 gene polymorphisms in malignancies.Molecular biology reports · 2021Review
- LRH1 Acts as an Oncogenic Driver in Human Osteosarcoma and Pan-Cancer.Frontiers in cell and developmental biology · 2021Article
- Identification of lncRNA-miRNA-mRNA Networks Linked to Non-small Lung Cancer Resistance to Inhibitors of Epidermal Growth Factor Receptor.Frontiers in genetics · 2021Article
- The expression and significance of mTORC1 in diabetic retinopathy.BMC ophthalmology · 2020Article
- Targeting 14-3-3ζ Overcomes Resistance to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in Lung Adenocarcinoma via BMP2/Smad/ID1 Signaling.Frontiers in oncology · 2020Article
- EHD1 impairs decidualization by regulating the Wnt4/β-catenin signaling pathway in recurrent implantation failure.EBioMedicine · 2019Article
- Low Expression of ASK1-Interacting Protein-1 Is Significantly Correlated with Tumor Angiogenesis and Poor Survival in Patients with Early Stage Non-Small Cell Lung Cancer.OncoTargets and therapy · 2019Article
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12 authors.
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Abstract
backgroundNon-small cell lung cancer (NSCLC) is a devastating disease with a heterogeneous prognosis, and the molecular mechanisms underlying tumor progression remain elusive. Mammalian Eps15 homology domain 1 (EHD1) plays a promotive role in tumor progression, but its role in cancer angiogenesis remains unknown. This study thus explored the role of EHD1 in angiogenesis in NSCLC.
methodsThe changes in angiogenesis were evaluated through human umbilical vein endothelial cell (HUVEC) proliferation, migration and tube formation assays. The impact of EHD1 on β2-adrenoceptor (β2AR) signaling was evaluated by Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR) analysis, and enzyme-linked immunosorbent assay (ELISA). The interaction between EHD1 and β2AR was confirmed by immunofluorescence (IF) and coimmunoprecipitation (Co-IP) experiments, and confocal microscopy immunofluorescence studies revealed that β2AR colocalized with the recycling endosome marker Rab11, which indicated β2AR endocytosis. Xenograft tumor models were used to investigate the role of EHD1 in NSCLC tumor growth.
resultsThe microarray analysis revealed that EHD1 was significantly correlated with tumor angiogenesis, and loss- and gain-of-function experiments demonstrated that EHD1 potentiates HUVEC proliferation, migration and tube formation. EHD1 knockdown inhibited β2AR signaling activity, and EHD1 upregulation promoted vascular endothelial growth factor A (VEGFA) and β2AR expression. Interestingly, EHD1 interacted with β2AR and played a novel and critical role in β2AR endocytic recycling to prevent receptor degradation. Aberrant VEGFA or β2AR expression significantly affected EHD1-mediated tumor angiogenesis. The proangiogenic role of EHD1 was confirmed in xenograft tumor models, and immunohistochemistry (IHC) analysis confirmed that EHD1 expression was positively correlated with VEGFA expression, microvessel density (MVD) and β2AR expression in patient specimens.
conclusionCollectively, the data obtained in this study suggest that EHD1 plays a critical role in NSCLC angiogenesis via β2AR signaling and highlight a potential target for antiangiogenic therapy.
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