PAI-1 leads to G1-phase cell-cycle progression through cyclin D3/cdk4/6 upregulation.

ABSTRACT:

Unlabelled

The canonical function of plasminogen activator inhibitor-1 (PAI-1/SERPINE1) is as an inhibitor of urokinase-type plasminogen activator for blood clot maintenance, but it is now also considered a pleiotropic factor that can exert diverse cellular and tumorigenic effects. However, the mechanism controlling its pleiotropic effects is far from being understood. To elucidate the tumorigenic role of PAI-1, we tested the effects of PAI-1 after manipulation of its expression or through the use of a small-molecule inhibitor, tiplaxtinin. Downregulation of PAI-1 significantly reduced cellular proliferation through an inability to progress from the G(0-G1) phase of the cell cycle. Accordingly, overexpression of PAI-1 augmented proliferation by encouraging S-phase entry. Biochemica

SUBMITTER: Giacoia EG 

PROVIDER: S-EPMC4064567 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature