Mechanisms Behind Skin Senescence Revealed

Findings published today in Cell Reports reveal important insights into the molecular mechanisms that underpin the body’s natural defenses against the development of skin cancer. The study, led by researchers at the Center for Genomic Regulation, offers new clues into the behavior of skin cancer at the cellular level, paving the way for potential new therapeutic targets to treat the disease.

“We found that the protein CSDE1 coordinates a complex chain of events that enable senescence in skin cells, significantly slowing down their function without causing death,” says Rosario Avolio, first author of the study. “The resulting cells act as a firewall against cancer, suppressing the formation of tumors.”

Researchers led by Fátima Gebauer carried out the study by collecting keratinocytes from mice, the most abundant type of skin cell in the epidermis. The group introduced genes that drive the formation of cancer, inducing the cells into a state of senescence. They found that when levels of CSDE1 were depleted, cells could not undergo senescence and became immortalized.

Further experiments revealed that when CSDE1-depleted cells were implanted under the skin of mice, they started forming malignant tumors. The authors found this striking because every treated mouse developed squamous cell carcinomas within 15 to 20 days, highlighting the importance of CSDE1 in tumor suppression. The researchers also discovered that CSDE1 promotes tumor suppression through two different mechanisms. 

“It was long thought that RNA-binding proteins are universal molecules that cells use for general housekeeping and that they cannot be targeted therapeutically. It is becoming increasingly clear that this is not true, and that this emerging field is critical for understanding human disease,” Gebauer concludes.