| 词条 | Neuropilin 1 |
| 释义 |
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. FunctionNRP1 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] InteractionsNeuropilin 1 has been shown to interact with Vascular endothelial growth factor A.[1][4] Implication in cancerNeuropilin 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 therapiesAs 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] References1. ^1 {{cite journal | vauthors = Soker S, Takashima S, Miao HQ, Neufeld G, Klagsbrun M | title = Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor | journal = Cell | volume = 92 | issue = 6 | pages = 735–45 | date = March 1998 | pmid = 9529250 | pmc = | doi = 10.1016/S0092-8674(00)81402-6 }} 2. ^{{cite journal | vauthors = Chen H, Chédotal A, He Z, Goodman CS, Tessier-Lavigne M | title = 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 | journal = Neuron | volume = 19 | issue = 3 | pages = 547–59 | date = September 1997 | pmid = 9331348 | pmc = | doi = 10.1016/S0896-6273(00)80371-2 }} 3. ^1 {{cite web | title = Entrez Gene: NRP1 neuropilin 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8829| accessdate = }} 4. ^{{cite journal | vauthors = Mamluk R, Gechtman Z, Kutcher ME, Gasiunas N, Gallagher J, Klagsbrun M | title = Neuropilin-1 binds vascular endothelial growth factor 165, placenta growth factor-2, and heparin via its b1b2 domain | journal = The Journal of Biological Chemistry | volume = 277 | issue = 27 | pages = 24818–25 | date = July 2002 | pmid = 11986311 | doi = 10.1074/jbc.M200730200 }} 5. ^1 {{cite journal | vauthors = 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 | title = Neuropilin-1 is upregulated in the adaptive response of prostate tumors to androgen-targeted therapies and is prognostic of metastatic progression and patient mortality | journal = Oncogene | volume = 36 | issue = 24 | pages = 3417–3427 | date = January 2017 | pmid = 28092670 | pmc = 5485179 | doi = 10.1038/onc.2016.482 }} 6. ^{{cite journal | vauthors = Fakhari M, Pullirsch D, Abraham D, Paya K, Hofbauer R, Holzfeind P, Hofmann M, Aharinejad S | title = Selective upregulation of vascular endothelial growth factor receptors neuropilin-1 and -2 in human neuroblastoma | journal = Cancer | volume = 94 | issue = 1 | pages = 258–63 | date = January 2002 | pmid = 11815985 | doi = 10.1002/cncr.10177 }} 7. ^{{cite journal | vauthors = Latil A, Bièche I, Pesche S, Valéri A, Fournier G, Cussenot O, Lidereau R | title = VEGF overexpression in clinically localized prostate tumors and neuropilin-1 overexpression in metastatic forms | journal = International Journal of Cancer | volume = 89 | issue = 2 | pages = 167–71 | date = March 2000 | pmid = 10754495 | doi = 10.1002/(SICI)1097-0215(20000320)89:2<167::AID-IJC11>3.0.CO;2-9 }} 8. ^{{cite journal | vauthors = Bachelder RE, Crago A, Chung J, Wendt MA, Shaw LM, Robinson G, Mercurio AM | title = Vascular endothelial growth factor is an autocrine survival factor for neuropilin-expressing breast carcinoma cells | journal = Cancer Research | volume = 61 | issue = 15 | pages = 5736–40 | date = August 2001 | pmid = 11479209 | doi = 10.3892/ijo.32.1.41 }} 9. ^{{cite journal | vauthors = Parikh AA, Fan F, Liu WB, Ahmad SA, Stoeltzing O, Reinmuth N, Bielenberg D, Bucana CD, Klagsbrun M, Ellis LM | title = Neuropilin-1 in human colon cancer: expression, regulation, and role in induction of angiogenesis | journal = The American Journal of Pathology | volume = 164 | issue = 6 | pages = 2139–51 | date = June 2004 | pmid = 15161648 | doi = 10.1016/s0002-9440(10)63772-8 | pmc=1615754}} 10. ^1 {{cite journal | vauthors = Hong TM, Chen YL, Wu YY, Yuan A, Chao YC, Chung YC, Wu MH, Yang SC, Pan SH, Shih JY, Chan WK, Yang PC | title = Targeting neuropilin 1 as an antitumor strategy in lung cancer | journal = Clinical Cancer Research | volume = 13 | issue = 16 | pages = 4759–68 | date = August 2007 | pmid = 17699853| doi = 10.1158/1078-0432.CCR-07-0001 }} 11. ^{{cite journal | vauthors = Miao HQ, Lee P, Lin H, Soker S, Klagsbrun M | title = Neuropilin-1 expression by tumor cells promotes tumor angiogenesis and progression | journal = FASEB Journal | volume = 14 | issue = 15 | pages = 2532–9 | date = December 2000 | pmid = 11099472 | doi = 10.1096/fj.00-0250com }} 12. ^1 {{cite journal | vauthors = Barr MP, Byrne AM, Duffy AM, Condron CM, Devocelle M, Harriott P, Bouchier-Hayes DJ, Harmey JH | title = A peptide corresponding to the neuropilin-1-binding site on VEGF(165) induces apoptosis of neuropilin-1-expressing breast tumour cells | journal = British Journal of Cancer | volume = 92 | issue = 2 | pages = 328–33 | date = January 2005 | pmid = 15655556| doi = 10.1038/sj.bjc.6602308 | pmc=2361857}} 13. ^{{cite web | title = Vegf peptides and their use (WO 2003082918 A1) | date = Oct 9, 2003| url = http://www.google.com/patents/WO2003082918A1?cl=en| format = patent}} 14. ^{{cite journal | vauthors = Gagnon ML, Bielenberg DR, Gechtman Z, Miao HQ, Takashima S, Soker S, Klagsbrun M | title = Identification of a natural soluble neuropilin-1 that binds vascular endothelial growth factor: In vivo expression and antitumor activity | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 6 | pages = 2573–8 | date = March 2000 | pmid = 10688880 | pmc = 15970 | doi = 10.1073/pnas.040337597 }} Further reading{{refbegin | 2}}
1 : Proteins |
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