ArticleScience signaling2017
The neuropilin 2 isoform NRP2b uniquely supports TGFβ-mediated progression in lung cancer.
Article in Science signaling, 2017. 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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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- Molecular biology of targeting lymphangiogenesis in cancer: Therapeutic strategies and future promise.Fundamental research · 2026Review
- Semaphorin 3F inhibits breast cancer metastasis by regulating the Akt-mTOR and TGFβ signaling pathways via neuropilin-2.Scientific reports · 2025Article
- Advances in lymphatic metastasis of non-small cell lung cancer.Cell communication and signaling : CCS · 2024Review
- Orchestrating Resilience: How Neuropilin-2 and Macrophages Contribute to Cardiothoracic Disease.Journal of clinical medicine · 2024Review
- Role of Neuropilin-2-mediated signaling axis in cancer progression and therapy resistance.Cancer metastasis reviews · 2022Review
- Neuropilin (NRPs) Related Pathological Conditions and Their Modulators.International journal of molecular sciences · 2022Review
- Neuropilin-2 regulates androgen-receptor transcriptional activity in advanced prostate cancer.Oncogene · 2022Article
- Isoforms of Neuropilin-2 Denote Unique Tumor-Associated Macrophages in Breast Cancer.Frontiers in immunology · 2022Article
- TGF-β superfamily co-receptors in cancer.Developmental dynamics : an official publication of the American Association of Anatomists · 2022Review
- Neuropilin-2b facilitates resistance to tyrosine kinase inhibitors in non-small cell lung cancer.The Journal of thoracic and cardiovascular surgery · 2021Article
- Neuropilin-2 and Its Transcript Variants Correlate with Clinical Outcome in Bladder Cancer.Genes · 2021Article
- The enzymatic hydrolysates from deer sinew promote MC3T3-E1 cell proliferation and extracellular matrix synthesis by regulating multiple functional genes.BMC complementary medicine and therapies · 2021Article
- Neuropilin-2 Is Associated With Increased Hepatoblastoma Cell Viability and Motility.Frontiers in pediatrics · 2021Article
- Article
- Review
- Neuropilins in the Context of Tumor Vasculature.International journal of molecular sciences · 2019Review
- VEGF/Neuropilin Signaling in Cancer Stem Cells.International journal of molecular sciences · 2019Review
- Linking NRP2 With EMT and Chemoradioresistance in Bladder Cancer.Frontiers in oncology · 2019Article
- Regulation of PTEN expression by noncoding RNAs.Journal of experimental & clinical cancer research : CR · 2018Review
- Oligosaccharyltransferase Inhibition Overcomes Therapeutic Resistance to EGFR Tyrosine Kinase Inhibitors.Cancer research · 2018Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Neuropilins (NRP1 and NRP2) are co-receptors for heparin-binding growth factors and class 3 semaphorins. Different isoforms of NRP1 and NRP2 are produced by alternative splicing. We found that in non-small cell lung cancer (NSCLC) cell lines, transforming growth factor-β (TGFβ) signaling preferentially increased the abundance of NRP2b. NRP2b and NRP2a differ only in their carboxyl-terminal regions. Although the presence of NRP2b inhibited cultured cell proliferation and primary tumor growth, NRP2b enhanced cellular migration, invasion into Matrigel, and tumorsphere formation in cultured cells in response to TGFβ signaling and promoted metastasis in xenograft mouse models. These effects of overexpressed NRP2b contrast with the effects of overexpressed NRP2a. Hepatocyte growth factor (HGF)-induced phosphorylation of the kinase AKT was specifically promoted by NRP2b, whereas inhibiting the HGF receptor MET attenuated NRP2b-dependent cell migration. Unlike NRP2a, NRP2b did not bind the PDZ domain scaffolding protein GAIP carboxyl terminus-interacting protein (GIPC1) and only weakly recruited phosphatase and tensin homolog (PTEN), potentially explaining the difference between NRP2b-mediated and NRP2a-mediated effects. Analysis of NSCLC patient tumors showed that NRP2b abundance correlated with that of the immune cell checkpoint receptor ligand PD-L1 as well as with epithelial-to-mesenchymal transition (EMT) phenotypes in the tumors, acquired resistance to epidermal growth factor receptor (EGFR) inhibitors, disease progression, and poor survival in patients. NRP2b knockdown attenuated the acquisition of resistance to the EGFR inhibitor gefitinib in cultured NSCLC cells. Thus, in NSCLC, NRP2b contributed to the oncogenic response to TGFβ and correlated with tumor progression in patients.
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