Researchers have identified a protein that plays a key role in preventing skin cancer cells from dividing and multiplying.
Writing in the July 20 issue of Molecular Cell, a team at the University of Texas M.D. Anderson Cancer Center, reported that the protein IKKa prevented a vital "checkpoint" gene from shutting down and allowing cancer cells to spread.
The protein often is absent or only found at lower levels in a type of skin cancer cell.
IKKa is found at lower than normal levels in aggressive squamous cell carcinomas in both mice and humans. When operating normally, it allows the checkpoint gene 14-3-3o to respond to DNA damage in the cell. The gene usually creates a protein that blocks defective cells from dividing, allowing genetic errors to be repaired rather than copied.
Without IKKa proteins, the gene does not function optimally, and cells that multiply with damaged or abnormal genes are the root of cancer.
The interaction is part of the process of DNA methylation -- a process by which the work of a gene is chemically altered, but the gene itself is not damaged. Researchers look for ways to chemically turn the gene back on and restore its function.
The team inserted IKKa into deficient cells, which allowed the checkpoint gene to work again.
"What we've identified is a mechanism that promotes genetic instability in keratinocytes, a critical type of skin cell that makes up 90 percent of epidermal cells, during the development of human skin cancers," Yinling Hu, senior author of the paper and assistant professor in M.D. Anderson's department of carcinogenesis at the Science Park-Research Division in Smithville, Texas, said in a prepared statement. "Our finding opens a new avenue for identifying new therapeutic targets for battling cancer," Hu said.
The findings may have implications for a broad array of cancers, as the researchers noted that the checkpoint gene 14-3-3o is also shut dow n in cancerous epithelial cells. Epithelial cells are found in the outer layer of skin and in the linings of other body organs such as lungs, and the gastrointestinal, reproductive and urinary tracts.
HealthDay News, July 24, 2007