Biology:Neuropilin 1

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Neuropilin-1 is a protein that in humans is encoded by the NRP1 gene.[1][2][3] In humans, the neuropilin 1 gene is located at 10p11.22. This is one of two human neuropilins.

Function

NRP1 is a membrane-bound coreceptor to a tyrosine kinase receptor for both vascular endothelial growth factor (for example, VEGFA) and semaphorin (for example, SEMA3A) family members. NRP1 plays versatile roles in angiogenesis, axon guidance, cell survival, migration, and invasion.[supplied by OMIM][3]

Interactions

Neuropilin 1 has been shown to interact with Vascular endothelial growth factor A.[1][4]

Role in COVID-19

Research has shown that neuropilin 1 facilitates entry of SARS-CoV-2 into cells, making it a possible target for future antiviral drugs.[5][6]

Implication in cancer

Neuropilin 1 has been implicated in the vascularization and progression of cancers. NRP1 expression has been shown to be elevated in a number of human patient tumor samples, including brain, prostate, breast, colon, and lung cancers and NRP1 levels are positively correlated with metastasis.[7][8][9][10][11][12]

In prostate cancer NRP1 has been demonstrated to be an androgen-suppressed gene, upregulated during the adaptive response of prostate tumors to androgen-targeted therapies and a prognostic biomarker of clinical metastasis and lethal PCa.[7] In vitro and in vivo mouse studies have shown membrane bound NRP1 to be proangiogenic and that NRP1 promotes the vascularization of prostate tumors.[13]

Elevated NRP1 expression is also correlated with the invasiveness of non-small cell lung cancer both in vitro and in vivo.[12]

Target for cancer therapies

As a co-receptor for VEGF, NRP1 is a potential target for cancer therapies. A synthetic peptide, EG3287, was generated in 2005 and has been shown to block NRP1 activity.[14] EG3287 has been shown to induce apoptosis in tumor cells with elevated NRP1 expression.[14] A patent for EG3287 was filed in 2002 and approved in 2003.[15] As of 2015 there were no clinical trials ongoing or completed for EG3287 as a human cancer therapy.

Soluble NRP1 has the opposite effect of membrane bound NRP1 and has anti-VEGF activity. In vivo mouse studies have shown that injections of sNRP-1 inhibits progression of acute myeloid leukemia in mice.[16]

References

  1. ↑ 1.0 1.1 "Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor". Cell 92 (6): 735–45. March 1998. doi:10.1016/S0092-8674(00)81402-6. PMID 9529250. 
  2. ↑ "Neuropilin-2, a novel member of the neuropilin family, is a high affinity receptor for the semaphorins Sema E and Sema IV but not Sema III". Neuron 19 (3): 547–59. September 1997. doi:10.1016/S0896-6273(00)80371-2. PMID 9331348. 
  3. ↑ 3.0 3.1 "Entrez Gene: NRP1 neuropilin 1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8829. 
  4. ↑ "Neuropilin-1 binds vascular endothelial growth factor 165, placenta growth factor-2, and heparin via its b1b2 domain". The Journal of Biological Chemistry 277 (27): 24818–25. July 2002. doi:10.1074/jbc.M200730200. PMID 11986311. 
  5. ↑ Cantuti-Castelvetri, Ludovico; Ojha, Ravi; Pedro, Liliana D.; Djannatian, Minou; Franz, Jonas; Kuivanen, Suvi; Meer, Franziska van der; Kallio, Katri et al. (13 November 2020). "Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity". Science 370 (6518): 856–860. doi:10.1126/science.abd2985. PMID 33082293. Bibcode: 2020Sci...370..856C. 
  6. ↑ "Neuropilin-1 drives SARS-CoV-2 infectivity, finds breakthrough study". MedicalXpress. https://medicalxpress.com/news/2020-10-neuropilin-sars-cov-infectivity-breakthrough.html. 
  7. ↑ 7.0 7.1 "Neuropilin-1 is upregulated in the adaptive response of prostate tumors to androgen-targeted therapies and is prognostic of metastatic progression and patient mortality". Oncogene 36 (24): 3417–3427. January 2017. doi:10.1038/onc.2016.482. PMID 28092670. 
  8. ↑ "Selective upregulation of vascular endothelial growth factor receptors neuropilin-1 and -2 in human neuroblastoma". Cancer 94 (1): 258–63. January 2002. doi:10.1002/cncr.10177. PMID 11815985. 
  9. ↑ "VEGF overexpression in clinically localized prostate tumors and neuropilin-1 overexpression in metastatic forms". International Journal of Cancer 89 (2): 167–71. March 2000. doi:10.1002/(SICI)1097-0215(20000320)89:2<167::AID-IJC11>3.0.CO;2-9. PMID 10754495. 
  10. ↑ "Vascular endothelial growth factor is an autocrine survival factor for neuropilin-expressing breast carcinoma cells". Cancer Research 61 (15): 5736–40. August 2001. PMID 11479209. 
  11. ↑ "Neuropilin-1 in human colon cancer: expression, regulation, and role in induction of angiogenesis". The American Journal of Pathology 164 (6): 2139–51. June 2004. doi:10.1016/s0002-9440(10)63772-8. PMID 15161648. 
  12. ↑ 12.0 12.1 "Targeting neuropilin 1 as an antitumor strategy in lung cancer". Clinical Cancer Research 13 (16): 4759–68. August 2007. doi:10.1158/1078-0432.CCR-07-0001. PMID 17699853. 
  13. ↑ "Neuropilin-1 expression by tumor cells promotes tumor angiogenesis and progression". FASEB Journal 14 (15): 2532–9. December 2000. doi:10.1096/fj.00-0250com. PMID 11099472. 
  14. ↑ 14.0 14.1 "A peptide corresponding to the neuropilin-1-binding site on VEGF(165) induces apoptosis of neuropilin-1-expressing breast tumour cells". British Journal of Cancer 92 (2): 328–33. January 2005. doi:10.1038/sj.bjc.6602308. PMID 15655556. 
  15. ↑ "Vegf peptides and their use (WO 2003082918 A1)" (patent). Oct 9, 2003. http://www.google.com/patents/WO2003082918A1?cl=en. 
  16. ↑ "Identification of a natural soluble neuropilin-1 that binds vascular endothelial growth factor: In vivo expression and antitumor activity". Proceedings of the National Academy of Sciences of the United States of America 97 (6): 2573–8. March 2000. doi:10.1073/pnas.040337597. PMID 10688880. Bibcode: 2000PNAS...97.2573G. 

Further reading



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