ArticleBreast cancer research : BCR2022
Neuropilin-1 is over-expressed in claudin-low breast cancer and promotes tumor progression through acquisition of stem cell characteristics and RAS/MAPK pathway activation.
Article in Breast cancer research : BCR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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26 citing papers in PubMed, 33 citations in OpenAlex.
- NCEH1 promotes breast cancer progression by regulating NRP1 and activating the TNF-α/NF-κB signalling pathway.Cell adhesion & migration · 2026Article
- An effective tumor-inhibiting siRNA delivery platform.Biochemical and biophysical research communications · 2026Article
- OTUD4 deubiquitination stabilizes EGFR and activates the PI3K/AKT pathway to promote the invasiveness of triple-negative breast cancer.Cell death & disease · 2026Article
- Improved protein binder design using β-pairing targeted RFdiffusion.Nature communications · 2026Article
- Vessels in Middle-Earth: meeting report from the 2025 Australasian Summit on Vascular Biology and Microcirculation.Vascular biology (Bristol, England) · 2026Article
- Crosstalk between NRP1 and autophagy in the tumor microenvironment: from molecular mechanisms to therapeutic targeting.Frontiers in immunology · 2026Review
- Bulk RNA sequencing dataset of Claudin-low breast cancer cell lines with Neuropilin-1 knockdown.Scientific data · 2025Article
- Systemic dual delivery of a tumor-inhibiting plasmid expressing p16 and shRaf.Biochemical and biophysical research communications · 2025Article
- Phenotypic plasticity and secretory heterogeneity in subpopulations derived from single cancer cell.Acta pharmaceutica Sinica. B · 2025Article
- Quantitative proteomics analysis of triple-negative breast cancers.NPJ precision oncology · 2025Article
- Neuropilin-1: A Multifaceted Target for Cancer Therapy.Current oncology (Toronto, Ont.) · 2025Review
- Semaphorin 3F inhibits breast cancer metastasis by regulating the Akt-mTOR and TGFβ signaling pathways via neuropilin-2.Scientific reports · 2025Article
- A Facile and Promising Delivery Platform for siRNA to Solid Tumors.Molecules (Basel, Switzerland) · 2024Article
- Periapical cemento-osseous dysplasia masquerading as asymptomatic chronic apical periodontitis in a Chinese woman: A case report.Clinical case reports · 2024Article
- Peptide PET Imaging: A Review of Recent Developments and a Look at the Future of Radiometal-Labeled Peptides in Medicine.Chemical & biomedical imaging · 2024Review
- Identification of novel pQTL-SNPs associated with lung adenocarcinoma risk: A multi-stage study.Cancer medicine · 2024Article
- Article
- Small molecule agents for triple negative breast cancer: Current status and future prospects.Translational oncology · 2024Review
- VEGFA/NRP-1/GAPVD1 axis promotes progression and cancer stemness of triple-negative breast cancer by enhancing tumor cell-macrophage crosstalk.International journal of biological sciences · 2024Article
- Neuropilin-1 Knockout and Rescue Confirms Its Role to Promote Metastasis in MDA-MB-231 Breast Cancer Cells.International journal of molecular sciences · 2023Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTriple-negative breast cancers (TNBC) have a relatively poor prognosis and responses to targeted therapies. Between 25 and 39% of TNBCs are claudin-low, a poorly differentiated subtype enriched for mesenchymal, stem cell and mitogen-activated signaling pathways. We investigated the role of the cell-surface co-receptor NRP1 in the biology of claudin-low TNBC.
methodsThe clinical prognostic value of NRP1 was determined by Kaplan-Meier analysis. GSVA analysis of METABRIC and Oslo2 transcriptomics datasets was used to correlate NRP1 expression with claudin-low gene signature scores. NRP1 siRNA knockdown was performed in MDA-MB-231, BT-549, SUM159 and Hs578T claudin-low cells and proliferation and viability measured by live cell imaging and DNA quantification. In SUM159 orthotopic xenograft models using NSG mice, NRP1 was suppressed by shRNA knockdown or systemic treatment with the NRP1-targeted monoclonal antibody Vesencumab. NRP1-mediated signaling pathways were interrogated by protein array and Western blotting.
resultsHigh NRP1 expression was associated with shorter relapse- and metastasis-free survival specifically in ER-negative BrCa cohorts. NRP1 was over-expressed specifically in claudin-low clinical samples and cell lines, and NRP1 knockdown reduced proliferation of claudin-low cells and prolonged survival in a claudin-low orthotopic xenograft model. NRP1 inhibition suppressed expression of the mesenchymal and stem cell markers ZEB1 and ITGA6, respectively, compromised spheroid-initiating capacity and exerted potent anti-tumor effects on claudin-low orthotopic xenografts (12.8-fold reduction in endpoint tumor volume). NRP1 was required to maintain maximal RAS/MAPK signaling via EGFR and PDGFR, a hallmark of claudin-low tumors.
conclusionsThese data implicate NRP1 in the aggressive phenotype of claudin-low breast cancer and offer a novel targeted therapeutic approach to this poor prognosis subtype.
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