Methionine Metabolism and Related Gene Expression Regulation in Cancers / 中国生物化学与分子生物学报

ABSTRACT

Methionine, an essential amino acid with a variety of physiological functions, plays an important role in the process of metabolic reprogramming of cancer cells. A large number of studies have found that there is dependence on exogenous methionine in different kinds of cancer cells, which is called the Hoffman effect. In vivo, methionine is metabolized through the methionine cycle, linking with the one carbon unit metabolism, folate cycle and the synthesis of many substances such as polyamine, glutathione, cysteine and nucleotide. Abnormity of methionine metabolism often occurs in tumors, accompanied by abnormal gene expression of methionine metabolism related enzymes, including methionine adenosyltransferase (MAT) and methylthioadenosine phosphorylase (MTAP). The abnormal expression of MAT and MTAP can lead to the abnormity of methionine cycle and the salvage pathway, resulting in the decrease of methyl donor S⁃adenosylmethionine (SAM) and the accumulation of methylthioadenosine (MTA) in cancer cells, which is associated with the genesis, progression and metastasis of tumors. Methionine restriction and target therapy derive from the changes of methionine metabolism and related gene expression separately. This review summarizes the changes of methionine⁃ dependent metabolism and the expression regulation of methionine metabolism related genes in cancer cells. Also, the new progress and difficulty in methionine⁃related cancer therapy is introduced. This review may provide new clues for the exploration of cancer therapy.