Epithelial-mesenchymal transition (EMT) has recently been studied to elucidate 
mechanisms of the liver metastatic process. We investigated EMT in the process 
of liver metastasis and the effects of chemotherapy on EMT cells as therapeutic 
strategy for colorectal liver metastasis. We used the CT26 murine colorectal 
carcinoma cell line to create an in vivo mouse liver metastasis model. Liver 
tumors were stained immuno-histochemically. Expression of proteins associated 
with TGF-β/Smad and hepatocyte growth factor (HGF)/c-Met pathways were 
investigated by western blotting. Cells with c-Met mRNA knockdown by siRNA 
techniques showed clearly reduced liver metastases compared with regular cells 
at 21 days. TGF-β and HGF induced EMT expression, but signal transduction was 
quite different. TGF-β induced ERK, but not Akt phosphory-lation. HGF mediated 
both ERK and Akt phosphorylation. Akt inhibitor blocked Akt phosphorylation but 
did not affect TGF-β-induced activation of ERK, Snail and Slug. U-0126 did not 
reduce Snail activity by TGF-β at a concentration to block ERK phosphorylation. 
However, Akt inhibitor and U-0126 completely inhibited HGF-induced Slug 
activation. 5-FU mediated cell death in the EMT process induced by TGF-β more 
effectively than HGF. ERK/Akt signaling, but not the Smad pathway, may be one of 
the main processes in HGF-induced EMT, despite the Smad pathway, but not 
ERK/Akt, being critical for TGF-β-induced EMT. The MAPK/Akt pathway is 
indispensable in HGF/c-Met signaling. The ERK/Akt pathway particularly may be 
critical in the HGF-induced EMT process. However, long-term use of 
chemotherapeutic agents may induce drug resistance and distant metastases 
through EMT-related signaling pathway activation.