SIRT6 protein may promote skin cancer development

SIRT6, a protein that suppresses liver and colon tumor growth, seems to have the opposite effect on skin cancer when combined with sun exposure.

Researchers found that SIRT6 promotes skin cancer development by turning on an enzyme that increases inflammation, proliferation and survival of sun-damaged skin cells.

SIRT6 helps repair DNA damage and is among a family of proteins called sirtuins. Sirtuins help regulate genomic stability and prevent genetic flaws associated with aging. Sun exposure seems to turn SIRT6 from cancer protector to cancer promoter.

“The opposing function of SIRT6 in skin cancer as compared with liver or colon cancers is likely due to the induction of SIRT6 by the carcinogenic UV rays in sunlight, and the unique tissue context in the skin,” says study author Yu-Ying He, Ph.D., assistant professor of medicine, University of Chicago. “We found more SIRT6 protein in sun-damaged squamous cell carcinoma cells than in healthy, sun-protected human skin. When we deleted SIRT6 from skin cells in mice, tumor development decreased.”

Dr. He and colleagues studied the effects of the inflammatory enzyme COX-2 on SIRT6. They found that increasing SIRT6 expression resulted in a greater abundance of COX-2. Inhibiting SIRT6 expression, led to a decrease in SIRT6 expression.

Ultraviolet-B light exposure triggered an increase in SIRT6 expression in skin cells. COX-2 production followed, leading to skin cancer development. SIRT6, she says, could be a target for skin cancer prevention.

“Natural compounds or safe pharmaceutical agents that revert sun-induced SIRT6 expression would be attractive approaches for topical or dietary applications. This may be particularly (helpful) for patients at high risk of skin cancer, including those with a skin cancer history or chronic sun damage,” Dr. He says.

The findings were published online Oct. 15 in Cancer Research. 

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