TI - SIAH1 causes growth arrest and apoptosis in hepatoma cells through beta-catenin degradation -dependent and -independent mechanisms . AB - We have previously shown that expression of SIAH1 is frequently down-regulated in HCCs and associated with their advanced stages . It has been shown that SIAH1 functions in the phosphorylation -independent degradation of beta-catenin and induces apoptosis and growth arrest . To examine if the effects of SIAH1 overexpression depend on the altered beta-catenin signaling pathway , we transferred the SIAH1 gene into three hepatoma cell lines with different genetic backgrounds : HepG2 (mutant beta-catenin) , SNU475 (mutant AXIN1) , and Huh7 cells ( wild type beta-catenin and AXIN1 ) . SIAH1 significantly decreased aberrant beta-catenin signal in HepG2 and SNU475 cells and induced growth arrest and apoptosis . However , SIAH1 also induced apoptosis in Huh7 cells , which retained a normal membranous distribution pattern of beta-catenin . Immunoblotting study demonstrated that SIAH1 also reduces the amount of PEG10 protein , which is known to be frequently overexpressed in HCC and to promote cell proliferation . These data suggest that PEG10 is another target protein of SIAH1 to induce apoptosis in hepatoma cells . Our results should lead to a better understanding of the relationship between deregulation of beta-catenin signals and hepatocarcinogenesis . Further investigations into the mechanisms by which SIAH1 promotes apoptosis and suppresses cell growth should also allow for the discovery of new therapeutic strategies .