A Tumor Suppressor for Brain Cancer (IMAGE)
Caption
A model for the function of IDH1 in tumor suppression: When IDH1 enzyme activity is inhibited, its product, alpha-KG, is substantially reduced in tumor cells. It is known that alpha-KG is required for the modification and degradation of HIF-1alpha, a protein that has multiple functions, including promoting blood vessel formation and stimulating metabolism. In other words, when the IDH1 gene is mutated, alpha-KG production is decreased and HIF-1alpha is stabilized. Increased HIF-1alpha then stimulates angiogenesis (blood vessel formation), and helps tumor cells get more nutrients and oxygen. This provides an advantage for tumor cells to grow. Zhao et al. tested and confirmed these steps in a cultured system, as well as verified increased HIF-1alpha in tumors. This image accompanied the report, “Glioma-Derived Mutations in IDH1 Dominantly Inhibit IDH1 Catalytic Activity and Induce HIF-1alpha," by S. Zhao and colleagues appearing in the April 10, 2009, issue of Science.
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