Purinergic antiplatelet-treated colon cancer cells induce SERPINE1 and MAPK-MMP1 signaling pathways associated with metastasis.

ABSTRACT: Contrary to many reports that antiplatelet agents inhibit cancer growth and metastasis, reports of increased mortality from the development of new solid tumors in patients receiving long-term antiplatelet therapy raise questions about the effects of antiplatelet agents on cancer. Therefore, we have investigated the direct effects on cancer cells in the absence of platelets, assuming long-term antiplatelet therapy. Treatment of cancer cells with four antiplatelet reagents (aspirin and three P2Y12 inhibitors: clopidogrel, prasugrel, and ticagrelor) inhibited the proliferation of cancer cells, similar to the results of previous studies. Surprisingly, there was no difference in the aspirin-treated group, but the motility of cancer cells was significantly increased when treated with purinergic P2Y12 inhibitors. Therefore, gene expression profiles were examined to investigate the effect of antiplatelet reagents on cancer cell mobility. As a result, SERPINE1 was identified as a common gene associated with cancer cell motility and cell death in three groups. SERPINE1 increased by antiplatelet reagent treatment was found to be involved in cell mobility by activating FAK-p38-MMP1. These results show that purine antiplatelet reagents reduce cancer cell proliferation but increase cell motility by inducing SERPINE1 and MAPK-MMP1 signaling pathways. Therefore, we suggest that SERPINE1 could be used as a new target gene for the development and metastasis of cancer in patients with long-term antiplatelet therapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE153127 | GEO | 2022/09/20

REPOSITORIES: GEO