Targeting VEGF–neuropilin interactions: a promising antitumor strategy

Peng, Kewen; Bai, Ying; Zhu, Qihua; Xu, Yungen

doi:10.1016/j.drudis.2018.10.004

Cited by 45 publications

(47 citation statements)

References 62 publications

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“…Cluster analysis within astrocytoma samples listed only VEGF and NRP1 within one complex. The corresponding proteins have been identified to interact in tumor biology and suggested as antitumor targets [78]. The only result from StringDB based graphs for possible protein complexes within glioblastoma multiforme listed HER2 and several RAS proto-oncogenes.…”

Section: Discussionmentioning

confidence: 99%

Open Data for Differential Network Analysis in Glioma

Jean-Quartier¹,

Jeanquartier²,

Holzinger³

2020

IJMS

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The complexity of cancer diseases demands bioinformatic techniques and translational research based on big data and personalized medicine. Open data enables researchers to accelerate cancer studies, save resources and foster collaboration. Several tools and programming approaches are available for analyzing data, including annotation, clustering, comparison and extrapolation, merging, enrichment, functional association and statistics. We exploit openly available data via cancer gene expression analysis, we apply refinement as well as enrichment analysis via gene ontology and conclude with graph-based visualization of involved protein interaction networks as a basis for signaling. The different databases allowed for the construction of huge networks or specified ones consisting of high-confidence interactions only. Several genes associated to glioma were isolated via a network analysis from top hub nodes as well as from an outlier analysis. The latter approach highlights a mitogen-activated protein kinase next to a member of histondeacetylases and a protein phosphatase as genes uncommonly associated with glioma. Cluster analysis from top hub nodes lists several identified glioma-associated gene products to function within protein complexes, including epidermal growth factors as well as cell cycle proteins or RAS proto-oncogenes. By using selected exemplary tools and open-access resources for cancer research and differential network analysis, we highlight disturbed signaling components in brain cancer subtypes of glioma.

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Section: Discussionmentioning

confidence: 99%

Open Data for Differential Network Analysis in Glioma

Jean-Quartier¹,

Jeanquartier²,

Holzinger³

2020

IJMS

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“…Although many studies have revealed the importance of VEGF-NRP signaling in tumor cells, independently of its role in angiogenesis (5), its contribution to DNA repair mechanisms is significant. Of note, VEGF-NRP signaling has been implicated in drug resistance in multiple tumors, but satisfying mechanisms have been elusive (9,(48)(49)(50). Given that efficient HR is a key Fig.…”

Section: Discussionmentioning

confidence: 99%

The VEGF receptor neuropilin 2 promotes homologous recombination by stimulating YAP/TAZ-mediated Rad51 expression

Elaimy

Amante

Zhu

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Vascular endothelial growth factor (VEGF) signaling in tumor cells mediated by neuropilins (NRPs) contributes to the aggressive nature of several cancers, including triple-negative breast cancer (TNBC), independently of its role in angiogenesis. Understanding the mechanisms by which VEGF–NRP signaling contributes to the phenotype of such cancers is a significant and timely problem. We report that VEGF–NRP2 promote homologous recombination (HR) in BRCA1 wild-type TNBC cells by contributing to the expression and function of Rad51, an essential enzyme in the HR pathway that mediates efficient DNA double-strand break repair. Mechanistically, we provide evidence that VEGF–NRP2 stimulates YAP/TAZ-dependent Rad51 expression and that Rad51 is a direct YAP/TAZ–TEAD transcriptional target. We also discovered that VEGF–NRP2–YAP/TAZ signaling contributes to the resistance of TNBC cells to cisplatin and that Rad51 rescues the defects in DNA repair upon inhibition of either VEGF–NRP2 or YAP/TAZ. These findings reveal roles for VEGF–NRP2 and YAP/TAZ in DNA repair, and they indicate a unified mechanism involving VEGF–NRP2, YAP/TAZ, and Rad51 that contributes to resistance to platinum chemotherapy.

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“…NRP1 and NRP2 are co-receptors that bind to and interact with a variety of growth factors (17,18). NRP1 is a transmembrane glycoprotein that binds to various extracellular ligands, including class III/IV semaphorins (19), certain isoforms of vascular endothelial growth factor (VEGF) (20), TGF-β1 (15), and platelet-derived growth factor (PDGF) (21). A previous study by the authors demonstrated that the expression of NRP1 was high in NSCLC tissues and was associated with a poorer survival of patients (22).…”

Section: Neuropilin 1 Modulates Tgf-β1-induced Epithelial-mesenchymalmentioning

confidence: 99%

Neuropilin 1 modulates TGF‑β1‑induced epithelial‑mesenchymal transition in non‑small cell lung cancer

Ding

et al. 2019

Int J Oncol

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Previously, the authors reported that neuropilin-1 (NRP1) was significantly increased and acted as a vital promoter in the metastasis of non-small cell lung cancer (NSCLC). However, the regulatory mechanism of NRP1 in NSCLC cell migration and invasion remained unclear. The present study aimed to explore the regulatory mechanism of NRP1 in the transforming growth factor-β (TGF-β) 1-induced migration and invasion of NSCLC cells. The expression level of NRP1 was determined by RT-qPCR analysis in human tissue samples with or without lymph node metastasis. Transwell assay and wound healing assay were conducted to determine the cell migration. Lentivirus-mediated stable knockdown and overexpression of NRP1 cell lines were constructed. Exogenous TGF-β1 stimulation, SIS3 treatment, western blot analysis and in vivo metastatic model were utilized to clarify the underlying regulatory mechanisms. The results demonstrated that the expression of NRP1 was increased in metastatic NSCLC tissues. NRP1 promoted NSCLC metastasis in vitro and in vivo. The Transwell assays, wound healing assays and western blot analysis revealed that the knockdown of NRP1 significantly inhibited TGF-β1-mediated EMT and migratory and invasive capabilities of NSCLC. Furthermore, the overexpression of NRP1 weakened the inhibitory effect of SIS3 on the NSCLC migration and invasion. Co-IP assay revealed that NRP1 interacted with TGFβRII to induce EMT. On the whole, the findings of this study demonstrated that NRP1 was overexpressed in metastatic NSCLC tissues. NRP1 could contributes to TGF-β1-induced EMT and metastasis in NSCLC by binding with TGFβRII.

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Targeting VEGF–neuropilin interactions: a promising antitumor strategy

Cited by 45 publications

References 62 publications

Open Data for Differential Network Analysis in Glioma

Open Data for Differential Network Analysis in Glioma

The VEGF receptor neuropilin 2 promotes homologous recombination by stimulating YAP/TAZ-mediated Rad51 expression

Neuropilin 1 modulates TGF‑β1‑induced epithelial‑mesenchymal transition in non‑small cell lung cancer

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