The FasL-Fas couple is a general death mediator whose activated signals lead to 
caspase-8 activation and apoptosis in adult hepatocytes. Suppression of 
caspase-8 activation and cell death is a protective mechanism modulated by the 
FLICE-Like Inhibitory Protein (FLIP). Although hepatocyte growth factor (HGF) 
and its receptor Met are known to mediate cell survival in developing livers, 
the molecular mechanisms involved in this process are poorly understood. We show 
here that Met activation by HGF impairs Fas-triggered apoptosis of primary 
embryonic hepatocytes and cell survival correlates with inhibition of caspase-8 
and caspase-3 activities. Furthermore, we found that HGF treatment prevents 
degradation of FLIPL triggered by Fas activation. In contrast to this, Met 
activation does not modulate FLIPL levels and its stability in untreated cells, 
thus showing the specificity of this regulatory mechanism for embryonic 
hepatocyte survival. Knocking down FLIP expression abolishes the ability of Met 
to inhibit Fas-triggered hepatocyte death, demonstrating the functional 
requirement of FLIP in HGF anti-apoptotic signals. By combining genetic and 
pharmacological approaches, we also demonstrate that the PI3K-Akt pathway is 
required in embryonic hepatocytes to prevent Fas-triggered FLIP degradation and 
death. Thus, Met acting on PI3K and Akt ensures high levels of FLIPL, and 
disruption of this pathway contributes to hepatic apoptosis and possibly to 
Fas-related liver diseases.