A study from University of Iowa has identified a key enzyme, known as TET1, may be an important target for cancer diagnostic and treatment. It gives a deeper understanding of how K-Ras turns off tumor suppressor genes. This finding was published on Cell Reports.
Mutations in the K-Ras gene have long been known to one of the main cause of cancer. K-Ras promotes cancer formation not only by driving cell growth and division, but also by turning off protective tumor suppressor genes, which normally limit uncontrolled cell growth and cause damaged cells to self-destruct.
In this study, researchers found that one of the ways tumor suppressor genes become methylated when K-Ras is activated is that an ‘eraser ‘ normally expressed in non-malignant cells. But when K-Ras is activated, the eraser is silenced, leading to accumulation of silencing methyl marks “the enzyme TET1″ is no longer expressed. Besides, adding TET1 back to these cells reactivates tumor suppressor genes and is enough to reduce their abnormal proliferation. Also, removing K-Ras signaling from cancer cells is enough to make them cancerous again, even without K-Ras.
This new finding could help physicians decide which treatments are most likely to work for a patient’s tumor. It pinpoints the pathway within the K-Ras biochemical cascade where the TET1 enzyme is silenced. Inhibitor drugs are available that block this pathway. The ability to reactivate TET1 gene expression in tumor cells may also be a way to test the therapeutic potential of new compounds being developed for cancer treatment.