Tumor initiating cells rely on methionine metabolism

  Understanding cell metabolism has great potential to develop new therapies for cancer metabolic pathways. Compared with normal tissues, the metabolic pathways of tumor cells have changed. However, cancer cells in tumors are heterogeneous, and tumor-inducing cells (TIC) are important therapeutic targets, but their metabolic properties are not yet clear.

  In order to understand the changes in metabolism, researchers from the Institute of Genomics, Nanyang Technological University, National University of Singapore and the Agency for Science and Technology Research of Singapore conducted TIC metabolism and metabolite tracking analysis. The results show that TIC is very high. MAT2A-driven methionine cycle activity level and methylation rate. Researchers have found that high methionine cycle activity causes the consumption of methionine to far exceed its regeneration, leading to exogenous methionine poisoning. By using drugs that block the methionine cycle (even if it is transient), the researchers found that these cells can weaken their ability to cause tumors. In addition, researchers have demonstrated that methionine circulating flux has a specific effect on the epigenetic state of cancer cells and promotes tumor development. Generally, methionine cycle enzymes are also expressed in large amounts in other types of tumors, and the expression of MAT2A affects the sensitivity of certain cancer cells to treatment inhibition.