AKT signaling is involved in protumorigenic function of MDM4 in human hepatocellular carcinoma

Compared to other cancers mutational inactivation of p53 is rare in hepatocellular carcinoma (HCC) in Western countries. The p53-interacting factors MDM4 and MDM2 are the main p53 regulators. 1q gains promote the upregulation of MDM4 in HCCs. However, these are not sufficient to explain the increased MDM4 activity observed in HCCs with balanced MDM4 gene locus. AKT1/2 are tyrosine kinases that promote cell survival. Here we show that AKT signaling is involved in the posttranscriptional stabilization of MDM4 protein in human HCC in vitro. Using a specific PI3K inhibitor or siRNAs targeting AKT1/2 in HCC cell line…