Aspirin prevention of cancer metastasis (WP5518)

Homo sapiens

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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)..

Authors

Eric Weitz

Activity

last edited

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

cancer pathway acetylsalicylic acid drug pathway

Cell Type Ontology

T cell neoplastic cell platelet

Disease Ontology

cancer

Participants
Query Drugst.One

Label Type Compact URI Comment
Aspirin Metabolite chebi:15365
PGH2 Metabolite chebi:15554
TXA2 Metabolite chebi:15627
GDP Metabolite chebi:17552
GTP Metabolite chebi:15996
PTGS1 GeneProduct ensembl:ENSG00000095303
TBXAS1 GeneProduct ensembl:ENSG00000059377
TBXA2R GeneProduct ensembl:ENSG00000006638
GNA12 GeneProduct ensembl:ENSG00000146535
TRG GeneProduct ensembl:6965
GNA13 GeneProduct ensembl:ENSG00000120063
ARHGEF1 GeneProduct ensembl:ENSG00000076928
RHOA GeneProduct ensembl:ENSG00000067560
TRA GeneProduct ncbigene:6955
TRB GeneProduct ncbigene:6957
TRD GeneProduct ncbigene:6964

References

  1. Aspirin prevents metastasis by limiting platelet TXA2 suppression of T cell immunity. Yang J, Yamashita-Kanemaru Y, Morris BI, Contursi A, Trajkovski D, Xu J, et al. Nature. 2025 Mar 5;10.1038/s41586-025-08626–7. PubMed Europe PMC Scholia