NRP1-triggered signaling pathways in pancreatic cancer (Homo sapiens)

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7, 12123, 73, 712731, 4, 113137734114, 7111, 4, 114, 1179391117, 119311117711141184310374, 7NucleusMigration, InvasionCell proliferationMetastasisEpithelial-mesenchymal transition(EMT)FibrosisEMT regulationSEMA3ACDH2CDH1NRP1SMAD2SMAD3GSK3NRP1AKT2SNAI1PLXNA4SMAD4PLXNA2NRP1NRP1HGFPI3KMiR-141NFKB1CD31METCDK2FAKZincMMP9MEK1ZIP4ERK1CDH5MMP2EGFp27COL1A2PLXNA1cyclin E1RAC1AKT1AKT3PP7PP7, 12PP11, 127, 12P711PEGFRNRP1ERK2MEK2PPSRCp130CasTGF-beta ReceptorTGFBR1TGFB3PTGFB1NRP1TGFB2TGFBR2TGFBR3PTGF-betaPCell cycle regulationSNAI2CTGFCOL1A1NRP1 regulationVEGF ReceptorVEGFR1VEGFANRP1VEGFR2VEGFAxon guidanceNFKB2RELARELBRELcyclin E2


This pathway model provides a holistic overview of the various signalling pathways which promote pancreatic cancer with the direct involvment of neuropilin 1, commonly known as NRP1. The multifaceted role of NRP1 in pancreatic ductal adenocarcinoma (PDAC) constitutes it as a promising therapeutic target for the fatal disease. The curation of the model was conducted by using the review done by Matkar et al. as a starting point and combining information gathered by several other studies investigating this particular phenomenon.

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  1. Donahue T, Hines OJ; ''The ZIP4 pathway in pancreatic cancer.''; Cancer Biol Ther, 2010 PubMed Europe PMC Scholia
  2. Zhu H, Jiang X, Zhou X, Dong X, Xie K, Yang C, Jiang H, Sun X, Lu J; ''Neuropilin-1 regulated by miR-320 contributes to the growth and metastasis of cholangiocarcinoma cells.''; Liver Int, 2018 PubMed Europe PMC Scholia
  3. Matkar PN, Singh KK, Rudenko D, Kim YJ, Kuliszewski MA, Prud'homme GJ, Hedley DW, Leong-Poi H; ''Novel regulatory role of neuropilin-1 in endothelial-to-mesenchymal transition and fibrosis in pancreatic ductal adenocarcinoma.''; Oncotarget, 2016 PubMed Europe PMC Scholia
  4. Li L, Jiang X, Zhang Q, Dong X, Gao Y, He Y, Qiao H, Xie F, Xie X, Sun X; ''Neuropilin-1 is associated with clinicopathology of gastric cancer and contributes to cell proliferation and migration as multifunctional co-receptors.''; J Exp Clin Cancer Res, 2016 PubMed Europe PMC Scholia
  5. Prud'homme GJ, Glinka Y; ''Neuropilins are multifunctional coreceptors involved in tumor initiation, growth, metastasis and immunity.''; Oncotarget, 2012 PubMed Europe PMC Scholia
  6. Lu D, Shang G, He X, Bai XC, Zhang X; ''Architecture of the Sema3A/PlexinA4/Neuropilin tripartite complex.''; Nat Commun, 2021 PubMed Europe PMC Scholia
  7. Ma L, Zhai B, Zhu H, Li W, Jiang W, Lei L, Zhang S, Qiao H, Jiang X, Sun X; ''The miR-141/neuropilin-1 axis is associated with the clinicopathology and contributes to the growth and metastasis of pancreatic cancer.''; Cancer Cell Int, 2019 PubMed Europe PMC Scholia
  8. Yoshida A, Shimizu A, Asano H, Kadonosono T, Kondoh SK, Geretti E, Mammoto A, Klagsbrun M, Seo MK; ''VEGF-A/NRP1 stimulates GIPC1 and Syx complex formation to promote RhoA activation and proliferation in skin cancer cells.''; Biol Open, 2015 PubMed Europe PMC Scholia
  9. Müller MW, Giese NA, Swiercz JM, Ceyhan GO, Esposito I, Hinz U, Büchler P, Giese T, Büchler MW, Offermanns S, Friess H; ''Association of axon guidance factor semaphorin 3A with poor outcome in pancreatic cancer.''; Int J Cancer, 2007 PubMed Europe PMC Scholia
  10. Zachary IC, Frankel P, Evans IM, Pellet-Many C; ''The role of neuropilins in cell signalling.''; Biochem Soc Trans, 2009 PubMed Europe PMC Scholia
  11. Matkar PN, Jong ED, Ariyagunarajah R, Prud'homme GJ, Singh KK, Leong-Poi H; ''Jack of many trades: Multifaceted role of neuropilins in pancreatic cancer.''; Cancer Med, 2018 PubMed Europe PMC Scholia
  12. Matsushita A, Götze T, Korc M; ''Hepatocyte growth factor-mediated cell invasion in pancreatic cancer cells is dependent on neuropilin-1.''; Cancer Res, 2007 PubMed Europe PMC Scholia


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120537view18:42, 12 December 2021Nadiapan1
120532view19:20, 11 December 2021Nadiapan1
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120520view15:45, 10 December 2021Mkutmonfix identifier
120519view15:43, 10 December 2021Mkutmonupdate identifiers
120518view15:28, 10 December 2021Mkutmonupdate identifiers
120517view15:23, 10 December 2021Mkutmonupdate identifiers
120516view15:09, 10 December 2021Mkutmonupdated colors
120515view15:07, 10 December 2021Mkutmonupdated layout
120512view12:31, 10 December 2021Nadiapan1
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120479view23:35, 7 December 2021Nadiapan1
120478view23:25, 7 December 2021Nadiapan1
120460view14:07, 6 December 2021Nadiapan1Modified description
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120444view22:15, 2 December 2021Nadiapan1
120426view15:06, 30 November 2021Nadiapan1
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120424view15:00, 30 November 2021Nadiapan1
120377view23:23, 29 November 2021EweitzModified title
120290view12:30, 24 November 2021Mkutmonadded missing ref information
120289view12:25, 24 November 2021Mkutmonfix references
120288view12:24, 24 November 2021Mkutmonfix publication references
120287view12:16, 24 November 2021MkutmonOntology Term : 'signaling pathway' added !
120286view12:16, 24 November 2021MkutmonOntology Term : 'pancreatic adenocarcinoma' added !
120285view12:14, 24 November 2021Nadiapan1New pathway

External references


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NameTypeDatabase referenceComment
AKT1ProteinP31749 (Uniprot-TrEMBL)
AKT2ProteinP31751 (Uniprot-TrEMBL)
AKT3ProteinQ9Y243 (Uniprot-TrEMBL)
CD31 ProteinP16284 (Uniprot-TrEMBL)
CDH1ProteinO14646 (Uniprot-TrEMBL)
CDH2ProteinO14647 (Uniprot-TrEMBL)
CDH5ProteinP33151 (Uniprot-TrEMBL)
CDK2ProteinP24941 (Uniprot-TrEMBL)
COL1A1GeneProductENSG00000108821 (Ensembl)
COL1A2GeneProductENSG00000164692 (Ensembl)
CTGFProteinP29279 (Uniprot-TrEMBL)
EGFProteinP01133 (Uniprot-TrEMBL)
EGFRProteinP00533 (Uniprot-TrEMBL)
ERK1ProteinP27361 (Uniprot-TrEMBL)
ERK2 ProteinP28482 (Uniprot-TrEMBL)
FAK ProteinQ05397 (Uniprot-TrEMBL)
GSK3ProteinP49840 (Uniprot-TrEMBL)
HGFProteinP14210 (Uniprot-TrEMBL)
MEK1 ProteinQ02750 (Uniprot-TrEMBL)
MEK2ProteinP36507 (Uniprot-TrEMBL)
METProteinP08581 (Uniprot-TrEMBL)
MMP2ProteinP08253 (Uniprot-TrEMBL)
MMP9ProteinP14780 (Uniprot-TrEMBL)
MiR-141RnaENSG00000207708 (Ensembl)
NFKB1ProteinP19838 (Uniprot-TrEMBL)
NFKB2ProteinQ00653 (Uniprot-TrEMBL)
NRP1ProteinENSG00000099250 (Ensembl)
NRP1ProteinO14786 (Uniprot-TrEMBL)
PI3KProtein2.7.1.137 (Enzyme Nomenclature)
PLXNA1ProteinQ9UIW2 (Uniprot-TrEMBL)
PLXNA2ProteinO75051 (Uniprot-TrEMBL)
PLXNA4ProteinQ9HCM2 (Uniprot-TrEMBL)
RAC1ProteinP63000 (Uniprot-TrEMBL)
RELAGeneProductQ04206 (Uniprot-TrEMBL)
RELBProteinQ01201 (Uniprot-TrEMBL)
RELProteinQ04864 (Uniprot-TrEMBL)
SEMA3AProteinQ14563 (Uniprot-TrEMBL)
SMAD2ProteinQ15796 (Uniprot-TrEMBL)
SMAD3ProteinP84022 (Uniprot-TrEMBL)
SMAD4ProteinQ13485 (Uniprot-TrEMBL)
SNAI1ProteinO95863 (Uniprot-TrEMBL)
SNAI2ProteinO43623 (Uniprot-TrEMBL)
SRCProteinP12931 (Uniprot-TrEMBL)
TGFB1ProteinP01137 (Uniprot-TrEMBL)
TGFB2ProteinP61812 (Uniprot-TrEMBL)
TGFB3ProteinP10600 (Uniprot-TrEMBL)
TGFBR1ProteinP36897 (Uniprot-TrEMBL)
TGFBR2ProteinP37173 (Uniprot-TrEMBL)
TGFBR3ProteinQ03167 (Uniprot-TrEMBL)
VEGFAProteinP15692 (Uniprot-TrEMBL)
VEGFR1ProteinP17948 (Uniprot-TrEMBL)
VEGFR2ProteinP35968 (Uniprot-TrEMBL)
ZIP4ProteinQ6P5W5 (Uniprot-TrEMBL)
ZincMetaboliteHMDB0015532 (HMDB)
cyclin E1ProteinP24864 (Uniprot-TrEMBL)
cyclin E2ProteinO96020 (Uniprot-TrEMBL)
p130Cas ProteinP56945 (Uniprot-TrEMBL)
p27ProteinP46527 (Uniprot-TrEMBL)

Annotated Interactions

No annotated interactions

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