Detail

USC Scientists Identify Epigenetic Events Critical To Cancer Cell Survival

Peter Jones, Ph.D., D.Sc. / photo by Van Urfalian


Scientists at the University of Southern California (USC) have identified a small number of specific genes that must be silenced in order for cancer cells to survive. Those genes may be good targets for new, more effective cancer treatments.

The discovery is detailed in the May 15 issue of Cancer Cell, a peer-reviewed scientific journal.

“We tracked down these genes and it’s the first time that it’s been done,” said Peter Jones, Ph.D., D.Sc., distinguished professor of urology, biochemistry and molecular biology at the Keck School of Medicine of USC and principal investigator of the study. “If these genes are not silenced through DNA methylation, the cancer cell dies.”

Normal, healthy cells have a life cycle whereas cancer cells do not. Cancer cells 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,” said 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.

Co-authors include Daniel D. De Carvalho, Shikhar Sharma, Jueng Soo You, Sheng-Fang Su, Phillippa C. Taberlay, Theresa K. Kelly, Xiaojing Yang and Gangning Liang, all from the Keck School of Medicine of USC. The study was supported by grant R37CA082422 from the National Institutes of Health’s National Cancer Institute.
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