Enzyme May Be Key To Cancer Progression In Many Tumors

Enzyme May Be Key To Cancer Progression In Many Tumors
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Mutations in the KRAS gene have long been known to cause cancer, and about one third of solid tumors have KRAS mutations or mutations in the KRAS pathway. KRAS 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. A new study provided a deeper understanding of how KRAS turns off tumor suppressor genes and identifies a key enzyme in the process. The findings, published online in the journal Cell Reports, suggest that this enzyme, known as TET1, may be an important target for cancer diagnostics and treatment.
In KRAS-driven cancers, tumor suppressor genes are turned off, or silenced, because the DNA that controls their expression is modified by methylation. The study shows that KRAS promotes this methylation-associated gene silencing by turning off the TET1 enzyme, which can remove methyl marks from DNA.
Cells that have become cancerous due to KRAS mutation proliferate abnormally and form colonies. The researchers found that adding TET1 back to these cells reactivates tumor suppressor genes and is enough to reduce their abnormal proliferation. In addition, removing KRAS signaling from cancer cells reduces the cells' malignancy, but taking TET1 away from these cells is enough to make them cancerous again, even without KRAS.
The findings, which implicate TET1 is an important player in the KRAS pathway, could help physicians decide which treatments are most likely to work for a patient's tumor. The new study pinpoints the pathway within the KRAS biochemical cascade where the TET1 enzyme is silenced. Inhibitor drugs are available that block this pathway.