Methionine adenosyltransferases in liver cancer

Figure 4 MAT genes expression pattern in normal liver and liver cancer. MAT1A is mainly expressed in normal liver by hepatocytes and bile duct epithelial cells; whereas MAT2A and MAT2B are expressed in extrahepatic tissues and by the non-parenchymal cells in the liver. During liver disease and malignant transformation there is a switch from MAT1A to MAT2A/MAT2B, being MAT2A and MAT2B the predominant MAT genes expressed in HCC and CCA. MAT1A maintains the differentiated state of the liver whilst MAT2A and MAT2B give proliferative and survival advantages to cancer cells. SAMe positively regulates MAT1A and negatively regulates MAT2A and MAT2B as well as feedback inhibits MATII. Accordingly, steady state SAMe levels are lower in patients with chronic liver disease and liver cancer due to the switch from MAT1A to MAT2A/MAT2B.