Cellular senescence is characterized by an irreversible cell cycle arrest that, 
when bypassed by mutation, contributes to cellular immortalization. Activated 
oncogenes induce a hyperproliferative response, which might be one of the 
senescence cues. We have found that expression of such an oncogene, Akt, causes 
senescence in primary mouse hepatoblasts in vitro. Additionally, AKT-driven 
tumors undergo senescence in vivo following p53 reactivation and show signs of 
differentiation. In another in vivo system, i.e., liver fibrosis, 
hyperproliferative signaling through AKT might be a driving force of the 
senescence in activated hepatic stellate cells. Senescent cells up-regulate and 
secrete molecules that, on the one hand, can reinforce the arrest and, on the 
other hand, can signal to an innate immune system to clear the senescent cells. 
The mechanisms governing senescence and immortalization are overlapping with 
those regulating self-renewal and differentiation. These respective control 
mechanisms, or their disregulation, are involved in multiple pathological 
conditions including fibrosis, wound healing, and cancer. Understanding 
extracellular cues that regulate these processes may enable new therapies for 
these conditions.