Aspirin prevention of cancer metastasis (Homo sapiens)

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ArcPathVisio Brace Ellipse EndoplasmicReticulum GolgiApparatus HexagonPathVisio MimDegradation Mitochondria Octagon PentagonPathVisio Rectangle RoundedRectangle SarcoplasmicReticulum TriangleEquilateralEast TrianglePathVisio none AntigenCOX1PlateletKinase signalingEffector functionsAspirinPTGS1Anti-metastatic immunityTBXAS1TBXA2RGNA12GNA13TRGTRATRBTRDPGH2TXA2TXA2ARHGEF1RHOAGDPRHOAGTPMetastatic cancer cellT cellThromboxane A2TPT cell receptorInactiveActiveName: Aspirin prevention of cancer metastasisOrganism: Homo sapiens


Description

Platelets generate TXA2, which binds to its receptor (TP) on T cells, initiating the activation of ARHGEF1, a guanine exchange factor that promotes the conversion of RhoA from its inactive GDP-bound state to its active GTP-bound form. This RhoA activation inhibits TCR-induced kinase pathways, T cell proliferation, and effector functions, ultimately suppressing anti-metastatic immunity. TXA2 production by platelets is COX1-dependent and can be blocked by aspirin or COX-1 selective inhibitors, which relieve T cells from TXA2-mediated suppression. Inspired by figure 14 in in [Yang et al. (2025)](https://www.nature.com/articles/s41586-025-08626-7)..

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Quality Tags

Image:Curated.pngApproved version

Ontology Terms

Pathway Ontology : classic metabolic pathway
 

Bibliography

  1. Yang J, Yamashita-Kanemaru Y, Morris BI, Contursi A, Trajkovski D, Xu J, Patrascan I, Benson J, Evans AC, Conti AG, Al-Deka A, Dahmani L, Avdic-Belltheus A, Zhang B, Okkenhaug H, Whiteside SK, Imianowski CJ, Wesolowski AJ, Webb LV, Puccio S, Tacconelli S, Bruno A, Di Berardino S, De Michele A, Welch HCE, Yu IS, Lin SW, Mitra S, Lugli E, van der Weyden L, Okkenhaug K, Saeb-Parsy K, Patrignani P, Adams DJ, Roychoudhuri R; ''Aspirin prevents metastasis by limiting platelet TXA(2) suppression of T cell immunity.''; Nature, 2025 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
137991
Approved
view02:04, 11 March 2025EweitzAdd supplemental labels
137990view01:57, 11 March 2025EweitzAdd cell type label
137989view01:55, 11 March 2025EweitzOntology Term : 'cancer' added !
137988view01:54, 11 March 2025EweitzOntology Term : 'T cell' added !
137987view01:53, 11 March 2025EweitzOntology Term : 'platelet' added !
137986view01:53, 11 March 2025EweitzOntology Term : 'neoplastic cell' added !
137985view01:53, 11 March 2025EweitzOntology Term : 'cancer pathway' added !
137984view01:52, 11 March 2025EweitzOntology Term : 'acetylsalicylic acid drug pathway' added !
137983view01:49, 11 March 2025EweitzIdentify metabolites
137982view01:46, 11 March 2025EweitzIdentify remaining genes
137981view01:41, 11 March 2025EweitzIdentify TCR genes: not in Ensembl, so use NCBI IDs
137896view13:03, 10 March 2025EweitzAdd literature reference
137895view12:13, 10 March 2025EweitzAdd interactions
137894view12:04, 10 March 2025EweitzAdd anti-metastatic immunity
137893view12:01, 10 March 2025EweitzNew pathway

External references

DataNodes

View all...
Name  ↓Type  ↓Database reference  ↓Comment  ↓
ARHGEF1GeneProductENSG00000076928 (Ensembl)
Anti-metastatic immunity
AspirinMetaboliteCHEBI:15365 (ChEBI)
Effector functionsPathway
GDPMetaboliteCHEBI:17552 (ChEBI)
GNA12GeneProductENSG00000146535 (Ensembl)
GNA13GeneProductENSG00000120063 (Ensembl)
GTPMetaboliteCHEBI:15996 (ChEBI)
Kinase signalingPathway
PGH2MetaboliteCHEBI:15554 (ChEBI)
PTGS1GeneProductENSG00000095303 (Ensembl)
RHOAGeneProductENSG00000067560 (Ensembl)
TBXA2RGeneProductENSG00000006638 (Ensembl)
TBXAS1GeneProductENSG00000059377 (Ensembl)
TRAGeneProduct6955 (Entrez Gene)
TRBGeneProduct6957 (Entrez Gene)
TRDGeneProduct6964 (Entrez Gene)
TRGGeneProduct6965 (Ensembl)
TXA2MetaboliteCHEBI:15627 (ChEBI)

Annotated Interactions

No annotated interactions

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