To kill cancer, don’t let genes go silent

USC (US) — Researchers have identified a small number of specific genes that need to be silenced for cancer cells to survive.

The discovery—detailed in the May 15 issue of Cancer Cell—means the genes may be good targets for new, more effective treatments.

“We tracked down these genes and it’s the first time that it’s been done,” says Peter Jones, professor of urology, biochemistry, and molecular biology at the University of Southern California (USC) and principal investigator of the study. “If these genes are not silenced through DNA methylation, the cancer cell dies.”


While normal, healthy cells have a life cycle, cancer cells don’t—they grow and multiply uncontrollably. Scientists have observed structural differences between the two, but it has been difficult to determine which differences drive the cell to avoid normal death and which are consequences of being a cancer cell. Jones and colleagues found that when certain genes in the cancer cell are silenced by DNA methylation, the cancer cell avoids death.

DNA methylation, or the addition of methyl groups to a gene, can change gene expression without changing the DNA sequence. This epigenetic process is potentially reversible, making the areas where it happens good targets for new treatments to be developed.

“We are interested in the gene drivers,” says Jones, an epigenetics pioneer whose 1980 discovery of the drug 5-azacytidine is now standard treatment for a pre-leukemia bone-marrow disorder. “In other words, we want to know what makes a cancer cell a cancer cell.”

Jones and colleagues examined the gene expression and DNA methylation profiles of colorectal cancer cells and normal healthy cells across the body. They found that the silencing of the IRAK3 gene was directly responsible for the increased expression of survivin, a gene that prevents or delays a cell’s death. They also found that cancer cells become dependent on the silencing of these genes through DNA methylation.

The National Cancer Institute at the National Institutes of Health supported the research.

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