Researchers from the Barcelona CRG discover how the first line of defense against skin cancer works

A team of researchers from Center for Genomic Regulation (CRG) of Barcelona have discovered the molecular mechanisms that support the the body’s natural defenses against the development of cancer of skin. The finding offers a clue to how this type of cancer behaves at the cellular level, thus facilitating the development of new treatments against the disease. The study, published in the journal Cell Reports, represents an important step forward in cancer research.

The CRG researchers, led by Fátima Gebauer, compiled mouse keratinocytes, the most abundant type of skin cell in the epidermis that can give rise to several types of skin cancer, and they introduced genes that promote the appearance of cancer to study the behavior of proteins in RNA.

The CSDE1 protein: key

The team of scientists discovered that the CSDE1 protein, which until now has always been associated with the formation of malignant tumors, can also act by blocking the growth and aggressiveness of tumors. This surprising finding opens the door to new types of research on this protein and its different methods of action since it acts in one way or another depending on the type of cell in which it is found. “CSDE1 is’ Dr. Jekyll and Mr. Hyde ‘of proteins. It has an unpredictable duality depending on the type of cell and tissue in which it is found, & rdquor; Gebauer explains. “We do not know why this protein promotes cancer in some cases and suppresses it in others. Finding the main cause of this phenomenon will have important implications for the discovery of new personalized treatments against cancer”.

CSDE1 is a type of protein that monitors RNA. These proteins stick to RNA, often at the time they are transcribed, and can change their function. One possible theory that explains why CSDE1 behaves differently in normal skin cells compared to cancer cells is the existence of slightly different variants in each cell type. This could affect the molecular machinery of the cell in different ways. Rosario Avolio, co-author of the study, affirms that it was discovered “that the CSDE1 protein coordinates a complex series of molecular mechanisms that drive the senescence in skin cells, slowing down its function without causing death. The senescent cells act as a firewall against cancer, suppressing the formation of tumors. ”

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An innovative study

The study, funded by the Ministry of Science and Innovation, the la Caixa Foundation, the Catalan Agency for Research and Universities and the Severo Ochoa Center of Excellence, is one of the few that analyzes the role of proteins that adhere to RNA in the establishment of cellular senescence, a process in which normal cells lose the ability to divide. “For a long time it was thought that proteins that adhere to RNA are universal molecules that cells use for general maintenance, and that furthermore they cannot be regulated for therapeutic benefit. It is becoming increasingly clear that this is not true and that it is an emerging field critical to understanding human disease, & rdquor; Gebauer concludes.