Neuropilin 1

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

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RefSeq (protein)

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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 (VEGF; MIM 192240) and semaphorin (see SEMA3A; MIM 603961) 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]

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.[5][6][7][8][9][10]

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.[5] In vitro and in vivo mouse studies have shown membrane bound NRP1 to be proangiogenic and that NRP1 promotes the vascularization of prostate tumors.[11]

Elevated NRP1 expression is also correlated with the invasiveness of non-small cell lung cancer both in vitro and in vivo.[10]

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.[12] EG3287 has been shown to induce apoptosis in tumor cells with elevated NRP1 expression.[12] A patent for EG3287 was filed in 2002 and approved in 2003.[13] 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.[14]

References

  1. 1.0 1.1 Soker S, Takashima S, Miao HQ, Neufeld G, Klagsbrun M (March 1998). "Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor". Cell. 92 (6): 735–45. doi:10.1016/S0092-8674(00)81402-6. PMID 9529250.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  2. Chen H, Chédotal A, He Z, Goodman CS, Tessier-Lavigne M (September 1997). "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. doi:10.1016/S0896-6273(00)80371-2. PMID 9331348.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  3. 3.0 3.1 "Entrez Gene: NRP1 neuropilin 1".<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  4. Mamluk R, Gechtman Z, Kutcher ME, Gasiunas N, Gallagher J, Klagsbrun M (July 2002). "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. doi:10.1074/jbc.M200730200. PMID 11986311.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  5. 5.0 5.1 Tse BW, Volpert M, Ratther E, Stylianou N, Nouri M, McGowan K, Lehman ML, McPherson SJ, Roshan-Moniri M, Butler MS, Caradec J, Gregory-Evans CY, McGovern J, Das R, Takhar M, Erho N, Alshalafa M, Davicioni E, Schaeffer EM, Jenkins RB, Ross AE, Karnes RJ, Den RB, Fazli L, Gregory PA, Gleave ME, Williams ED, Rennie PS, Buttyan R, Gunter JH, Selth LA, Russell PJ, Nelson CC, Hollier BG (January 2017). "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. doi:10.1038/onc.2016.482. PMID 28092670.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  6. Fakhari M, Pullirsch D, Abraham D, Paya K, Hofbauer R, Holzfeind P, Hofmann M, Aharinejad S (January 2002). "Selective upregulation of vascular endothelial growth factor receptors neuropilin-1 and -2 in human neuroblastoma". Cancer. 94 (1): 258–63. doi:10.1002/cncr.10177. PMID 11815985.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  7. Latil A, Bièche I, Pesche S, Valéri A, Fournier G, Cussenot O, Lidereau R (March 2000). "VEGF overexpression in clinically localized prostate tumors and neuropilin-1 overexpression in metastatic forms". International Journal of Cancer. 89 (2): 167–71. doi:10.1002/(SICI)1097-0215(20000320)89:2<167::AID-IJC11>3.0.CO;2-9. PMID 10754495.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  8. Bachelder RE, Crago A, Chung J, Wendt MA, Shaw LM, Robinson G, Mercurio AM (August 2001). "Vascular endothelial growth factor is an autocrine survival factor for neuropilin-expressing breast carcinoma cells". Cancer Research. 61 (15): 5736–40. doi:10.3892/ijo.32.1.41. PMID 11479209.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  9. Parikh AA, Fan F, Liu WB, Ahmad SA, Stoeltzing O, Reinmuth N, Bielenberg D, Bucana CD, Klagsbrun M, Ellis LM (June 2004). "Neuropilin-1 in human colon cancer: expression, regulation, and role in induction of angiogenesis". The American Journal of Pathology. 164 (6): 2139–51. doi:10.1016/s0002-9440(10)63772-8. PMC 1615754. PMID 15161648.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  10. 10.0 10.1 Hong TM, Chen YL, Wu YY, Yuan A, Chao YC, Chung YC, Wu MH, Yang SC, Pan SH, Shih JY, Chan WK, Yang PC (August 2007). "Targeting neuropilin 1 as an antitumor strategy in lung cancer". Clinical Cancer Research. 13 (16): 4759–68. doi:10.1158/1078-0432.CCR-07-0001. PMID 17699853.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  11. Miao HQ, Lee P, Lin H, Soker S, Klagsbrun M (December 2000). "Neuropilin-1 expression by tumor cells promotes tumor angiogenesis and progression". FASEB Journal. 14 (15): 2532–9. doi:10.1096/fj.00-0250com. PMID 11099472.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  12. 12.0 12.1 Barr MP, Byrne AM, Duffy AM, Condron CM, Devocelle M, Harriott P, Bouchier-Hayes DJ, Harmey JH (January 2005). "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. doi:10.1038/sj.bjc.6602308. PMC 2361857. PMID 15655556.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  13. "Vegf peptides and their use (WO 2003082918 A1)" (patent). Oct 9, 2003.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  14. Gagnon ML, Bielenberg DR, Gechtman Z, Miao HQ, Takashima S, Soker S, Klagsbrun M (March 2000). "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. doi:10.1073/pnas.040337597. PMC 15970. PMID 10688880.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>

Further reading

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  • Zachary I, Gliki G (February 2001). "Signaling transduction mechanisms mediating biological actions of the vascular endothelial growth factor family". Cardiovascular Research. 49 (3): 568–81. doi:10.1016/S0008-6363(00)00268-6. PMID 11166270.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • He Z, Tessier-Lavigne M (August 1997). "Neuropilin is a receptor for the axonal chemorepellent Semaphorin III". Cell. 90 (4): 739–51. doi:10.1016/S0092-8674(00)80534-6. PMID 9288753.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Giger RJ, Urquhart ER, Gillespie SK, Levengood DV, Ginty DD, Kolodkin AL (November 1998). "Neuropilin-2 is a receptor for semaphorin IV: insight into the structural basis of receptor function and specificity". Neuron. 21 (5): 1079–92. doi:10.1016/S0896-6273(00)80625-X. PMID 9856463.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Chen H, He Z, Bagri A, Tessier-Lavigne M (December 1998). "Semaphorin-neuropilin interactions underlying sympathetic axon responses to class III semaphorins". Neuron. 21 (6): 1283–90. doi:10.1016/S0896-6273(00)80648-0. PMID 9883722.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Takahashi T, Nakamura F, Jin Z, Kalb RG, Strittmatter SM (October 1998). "Semaphorins A and E act as antagonists of neuropilin-1 and agonists of neuropilin-2 receptors". Nature Neuroscience. 1 (6): 487–93. doi:10.1038/2203. PMID 10196546.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Rossignol M, Beggs AH, Pierce EA, Klagsbrun M (May 1999). "Human neuropilin-1 and neuropilin-2 map to 10p12 and 2q34, respectively". Genomics. 57 (3): 459–60. doi:10.1006/geno.1999.5790. PMID 10329017.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Makinen T, Olofsson B, Karpanen T, Hellman U, Soker S, Klagsbrun M, Eriksson U, Alitalo K (July 1999). "Differential binding of vascular endothelial growth factor B splice and proteolytic isoforms to neuropilin-1". The Journal of Biological Chemistry. 274 (30): 21217–22. doi:10.1074/jbc.274.30.21217. PMID 10409677.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Cai H, Reed RR (August 1999). "Cloning and characterization of neuropilin-1-interacting protein: a PSD-95/Dlg/ZO-1 domain-containing protein that interacts with the cytoplasmic domain of neuropilin-1". The Journal of Neuroscience. 19 (15): 6519–27. PMID 10414980.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Takahashi T, Fournier A, Nakamura F, Wang LH, Murakami Y, Kalb RG, Fujisawa H, Strittmatter SM (October 1999). "Plexin-neuropilin-1 complexes form functional semaphorin-3A receptors". Cell. 99 (1): 59–69. doi:10.1016/S0092-8674(00)80062-8. PMID 10520994.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Tamagnone L, Artigiani S, Chen H, He Z, Ming GI, Song H, Chedotal A, Winberg ML, Goodman CS, Poo M, Tessier-Lavigne M, Comoglio PM (October 1999). "Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates". Cell. 99 (1): 71–80. doi:10.1016/S0092-8674(00)80063-X. PMID 10520995.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Gagnon ML, Bielenberg DR, Gechtman Z, Miao HQ, Takashima S, Soker S, Klagsbrun M (March 2000). "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. doi:10.1073/pnas.040337597. PMC 15970. PMID 10688880.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Gluzman-Poltorak Z, Cohen T, Herzog Y, Neufeld G (June 2000). "Neuropilin-2 is a receptor for the vascular endothelial growth factor (VEGF) forms VEGF-145 and VEGF-165 [corrected]". The Journal of Biological Chemistry. 275 (24): 18040–5. doi:10.1074/jbc.M909259199. PMID 10748121.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Fuh G, Garcia KC, de Vos AM (September 2000). "The interaction of neuropilin-1 with vascular endothelial growth factor and its receptor flt-1". The Journal of Biological Chemistry. 275 (35): 26690–5. doi:10.1074/jbc.M003955200. PMID 10842181.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Rossignol M, Gagnon ML, Klagsbrun M (December 2000). "Genomic organization of human neuropilin-1 and neuropilin-2 genes: identification and distribution of splice variants and soluble isoforms". Genomics. 70 (2): 211–22. doi:10.1006/geno.2000.6381. PMID 11112349.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S (September 2000). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Reports. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Whitaker GB, Limberg BJ, Rosenbaum JS (July 2001). "Vascular endothelial growth factor receptor-2 and neuropilin-1 form a receptor complex that is responsible for the differential signaling potency of VEGF(165) and VEGF(121)". The Journal of Biological Chemistry. 276 (27): 25520–31. doi:10.1074/jbc.M102315200. PMID 11333271.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Walter JW, North PE, Waner M, Mizeracki A, Blei F, Walker JW, Reinisch JF, Marchuk DA (March 2002). "Somatic mutation of vascular endothelial growth factor receptors in juvenile hemangioma". Genes, Chromosomes & Cancer. 33 (3): 295–303. doi:10.1002/gcc.10028. PMID 11807987.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>