ArticleBiology open2015
VEGF-A/NRP1 stimulates GIPC1 and Syx complex formation to promote RhoA activation and proliferation in skin cancer cells.
Article in Biology open, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Neuropilin-1: A Multifaceted Target for Cancer Therapy.Current oncology (Toronto, Ont.) · 2025Review
- Histone deacetylase upregulation of neuropilin-1 in osteosarcoma is essential for pulmonary metastasis.Cancer letters · 2024Article
- NRP1 interacts with endoglin and VEGFR2 to modulate VEGF signaling and endothelial cell sprouting.Communications biology · 2024Article
- 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 (NRP1) Positively Regulates Adipogenic Differentiation in C3H10T1/2 Cells.International journal of molecular sciences · 2023Article
- Strength and duration of GIPC-dependent signaling networks as determinants in cancer.Neoplasia (New York, N.Y.) · 2021Review
- Autocrine Signaling of NRP1 Ligand Galectin-1 Elicits Resistance to BRAF-Targeted Therapy in Melanoma Cells.Cancers · 2020Article
- Targeting the Tumor Core: Hypoxia-Responsive Nanoparticles for the Delivery of Chemotherapy to Pancreatic Tumors.Molecular pharmaceutics · 2020Article
- The Role of Rho GTPases in VEGF Signaling in Cancer Cells.Analytical cellular pathology (Amsterdam) · 2020Review
- The Pivotal Roles of the Epithelial Membrane Protein Family in Cancer Invasiveness and Metastasis.Cancers · 2019Review
- Article
- NRP-1 interacts with GIPC1 and SYX to activate p38 MAPK signaling and cancer stem cell survival.Molecular carcinogenesis · 2019Article
- Neuropilins in the Context of Tumor Vasculature.International journal of molecular sciences · 2019Review
- The miR-141/neuropilin-1 axis is associated with the clinicopathology and contributes to the growth and metastasis of pancreatic cancer.Cancer cell international · 2019Article
- Epithelial membrane protein 1 promotes tumor metastasis by enhancing cell migration via copine-III and Rac1.Oncogene · 2018Article
- Neuropilin-1 upregulation elicits adaptive resistance to oncogene-targeted therapies.The Journal of clinical investigation · 2018Article
- NRP-1 interacts with GIPC1 and α6/β4-integrins to increase YAP1/∆Np63α-dependent epidermal cancer stem cell survival.Oncogene · 2018Article
- Vascular Endothelial Growth Factor-A Exerts Diverse Cellular Effects via Small G Proteins, Rho and Rap.International journal of molecular sciences · 2018Review
- Sema3d controls collective endothelial cell migration by distinct mechanisms via Nrp1 and PlxnD1.The Journal of cell biology · 2016Article
- Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma.The American journal of pathology · 2016Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuropilin-1 (NRP1) has been identified as a VEGF-A receptor. DJM-1, a human skin cancer cell line, expresses endogenous VEGF-A and NRP1. In the present study, the RNA interference of VEGF-A or NRP1 suppressed DJM-1 cell proliferation. Furthermore, the overexpression of the NRP1 wild type restored shNRP1-treated DJM-1 cell proliferation, whereas NRP1 cytoplasmic deletion mutants did not. A co-immunoprecipitation analysis revealed that VEGF-A induced interactions between NRP1 and GIPC1, a scaffold protein, and complex formation between GIPC1 and Syx, a RhoGEF. The knockdown of GIPC1 or Syx reduced active RhoA and DJM-1 cell proliferation without affecting the MAPK or Akt pathway. C3 exoenzyme or Y27632 inhibited the VEGF-A-induced proliferation of DJM-1 cells. Conversely, the overexpression of the constitutively active form of RhoA restored the proliferation of siVEGF-A-treated DJM-1 cells. Furthermore, the inhibition of VEGF-A/NRP1 signaling upregulated p27, a CDK inhibitor. A cell-penetrating oligopeptide that targeted GIPC1/Syx complex formation inhibited the VEGF-A-induced activation of RhoA and suppressed DJM-1 cell proliferation. In conclusion, this new signaling pathway of VEGF-A/NRP1 induced cancer cell proliferation by forming a GIPC1/Syx complex that activated RhoA to degrade the p27 protein.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.