Researchers have discovered a vulnerability of brain cancer cells that could offer a new opportunity for treatment of glioblastoma. Researchers find a subset of glioblastoma tumor cell that is dependent on a particular enzyme that breaks down the amino acid glycine. Without this enzyme, toxic metabolic byproducts build up inside the tumor cells, and they die. Blocking this enzyme in glioblastoma cells could offer a new way to combat this tumors. Loss of GLDC produces a disorder (nonketotic hyperglycinemia, which can cause severe mental retardation). The researchers found that GLDC is overexpressed only in glioblastoma cells with SHMT2 gene. Those cells are dependent on GLDC and when they lose it, they die. SHMT2 is expressed most highly in cancer cells and gives these cells a survival edge because it can indirectly influence the activity of PKM2 enzyme, that can impact whether cells can generate the material to build new cancer cells, but the same regulation also affects the consumption of oxygen. Without GLDC, glycine enters a different metabolic pathway that generates toxic products that accumulate and kill the cell. The finding also raises the possibility that these GLDC-dependent cells could be killed with drugs that block GLDC activity.
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