PURPOSE: The inhibitor of the apoptosis protein (IAP) family members, such as 
the X-linked IAP (XIAP), survivin, and livin, are essential for cell survival 
and antiapoptosis in colorectal cancer cells. We hypothesized that the 
hepatocyte growth factor (HGF) activation in colorectal cancer via c-Met 
receptor regulates IAP proteins through Akt signaling.
EXPERIMENTAL DESIGN: The level of IAPs and C-Met mRNA expression was assessed 
using a quantitative real-time reverse transcriptase-PCR (RT-PCR) assay on 
colorectal normal mucosa (n = 13), adenomas (n = 6), and colorectal cancer 
tumors (n = 50). The role of HGF/C-Met pathway through Akt and XIAP was 
investigated by small interfering RNA (siRNA) and quantitative RT-PCR analysis 
of colorectal cancer lines.
RESULTS: Of the IAPs, only XIAP showed significant correlation to tumor 
development and progression. XIAP mRNA level in primary colorectal cancer was 
significantly higher than that in colorectal normal mucosa (P = 0.01); liver 
metastases was significantly higher than primary colorectal cancer tumors (P = 
0.04); and primary colorectal cancer N1/N2 cases were significantly higher than 
N0 cases (P = 0.008). HGF stimulation of colorectal cancer lines enhanced XIAP 
mRNA expression but not other IAPs. Activation of XIAP expression by HGF was 
inhibited by siRNA targeting Akt1 and Akt2.
CONCLUSIONS: Activation of C-MET enhances XIAP through the Akt pathway. XIAP 
up-regulation was shown to be correlated to colorectal cancer tumor progression. 
The Akt-XIAP pathway may be a potential molecular target for regulating 
colorectal cancer progression.