Senescence, Wound Healing and Cancer. The PAI-1 Connection

Abstract

Prolonged propagation of primary diploid fibroblasts in culture activates an ageing process known as replicative senescence, which is considered to provide a barrier against oncogenic transformation. Remarkably, both cell autonomous tumor‑suppressive and cell nonautonomous tumor‑promoting effects of senescent cells have been reported. Recently, we described that the p53 target gene plasminogen activator inhibitor‑1 (PAI‑1) is an essential mediator of replicative senescence. PAI‑1 antagonizes the protease urokinase‑type plasminogen activator (uPA). Both are secreted factors and involved in heterotypic signaling processes such as wound healing, angiogenesis and metastasis. Both uPA and PAI‑1 are expressed in senescent cells and their relative abundance controls proliferation downstream of p53. Here, we present data that the effects of PAI‑1 and uPA in the senescence response are not strictly cell autonomous. We discuss these findings in the context of the emerging roles of PAI‑1 and uPA in heterotypic cellular signaling in senescence, wound healing and metastasis.