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
“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
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
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.