ArticleCellular oncology (Dordrecht, Netherlands)2024
Neuropilin-2 acts a critical determinant for epithelial-to-mesenchymal transition and aggressive behaviors of human head and neck cancer.
Article in Cellular oncology (Dordrecht, Netherlands), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 4 citations in OpenAlex.
- Neural-tumor interactions: bidirectional regulatory mechanisms and nervous system-targeted tumor therapeutic strategies.Biomarker research · 2026Review
- Cancer stem cells and drug resistance in cancer: molecular mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- Discovery and Cryo-EM-Guided Development of a Neuropilin-2-Binding Aptamer for Receptor Antagonism.Journal of the American Chemical Society · 2026Article
- MBsBMC cancer · 2025Article
- Cancer neuroscience in head and neck: interactions, modulation, and therapeutic strategies.Molecular cancer · 2025Review
- Neuropilin-2 Mediates Radioresistance in Nasopharyngeal Carcinoma via Wnt/β-Catenin Pathway.Cancer management and research · 2025Article
- Orchestrating Resilience: How Neuropilin-2 and Macrophages Contribute to Cardiothoracic Disease.Journal of clinical medicine · 2024Review
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeNeuropilin-2 (NRP2) is a multifunctional single-pass transmembrane receptor that binds to two disparate ligands, namely, vascular endothelial growth factors (VEGFs) and semaphorins (SEMAs). It is reportedly involved in neuronal and vascular development. In this study, we uncovered the exact functional role of NRP2 and its molecular mechanism during aggressive behaviors and lymph node (LN) metastasis in human head and neck cancer (HNC) and identified algal methanol extract as a potential novel NRP2 inhibitor.
methodsIn silico analyses and immunohistochemistry were used to investigate the relationship between NRP2 expression and the prognosis of HNC patients. The functional role of NRP2 on the proliferation, migration, invasion, and cancer stem cell (CSC) properties of HNC cells was examined by MTS, soft agar, clonogenic, transwell migration and invasion assays, and sphere formation assays. Signaling explorer antibody array, western blot, and qPCR were performed toward the investigation of a molecular mechanism that is related to NRP2.
resultsNRP2 was highly expressed in HNC and positively correlated with LN metastasis and advanced tumor stage and size in patients. Using loss- or gain-of-function approaches, we found that NRP2 promoted the proliferative, migratory, and invasive capacities of human HNC cells. Furthermore, NRP2 regulated Sox2 expression to exhibit aggressiveness and CSC properties of human HNC cells. We demonstrated that p90 ribosomal S6 kinase 1 (RSK1) elevates the aggressiveness and CSC properties of human HNC cells, possibly by mediating NRP2 and Sox2. Zeb1 was necessary for executing the NRP2/RSK1/Sox2 signaling pathway during the induction of epithelial-to-mesenchymal transition (EMT) and aggressive behaviors of human HNC cells. Moreover, the methanol extract of Codium fragile (MECF) repressed NRP2 expression, inhibiting the RSK1/Sox2/Zeb1 axis, which contributed to the reduction of aggressive behaviors of human HNC cells.
conclusionsThese findings suggest that NRP2 is a critical determinant in provoking EMT and aggressive behaviors in human HNC through the RSK1/Sox2/Zeb1 axis, and MECF may have the potential to be a novel NRP2 inhibitor for treating metastasis in HNC patients.
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