Methionine adenosyltransferases in liver cancer

Figure 3 Mechanisms of hepatocellular carcinoma development in the Mat1a knockout mouse. Multiple mechanisms are known to influence hepatocellular carcinoma development in the Mat1a-KO mouse. These include: oxidative stress due to lower GSH levels and higher CYP2E1 expression; mitochondrial dysfunction due to reduced PHB1 and increased mitochondrial CYP2E1 levels; increased sumoylation, stabilizing MATα2, which acts as a transcription factor to enhance BCL-2 transcription as well as directly interacting with BCL-2 leading to its stabilization; enhanced activation of the LKB1/AMPK pathway which leads to the cytoplasmic translocation of HuR from nucleus and subsequent stabilization of cyclins; aberrant activation of ERK which promotes uncontrolled cell growth; enhanced genomic instability due to DNA hypomethylation and impaired DNA repair machinery and increased number of liver cancer stem cells with tumorigenic potential.