"Coordinated post-transcriptional modulation of oncogene-induced senescence by UNR/CSDE1," according to a study published in Cell Reports (Jan. 11), shows an important molecular mechanism that underpins the body's natural protection against skin cancer development. This study sheds fresh light on the cellular activity of skin cancer and paves the path for the identification of potential new therapeutic targets.

"We found that the protein CSDE1 regulates a complex series of events that can senesce skin cells, significantly slowing their function without causing cell death," said Rosario Avolio, first author of the study and a CRG postdoctoral fellow, "and that the resulting the cells act as a firewall against cancer, preventing tumors from forming."

Researchers led by Fátima Gebauer of the Centre for Genomic Regulation (CRG) collected keratinocytes, the main constituent cells of the epidermis, from mice for this study. Keratinocytes can produce a variety of skin malignancies, including the two most frequent kinds of cancer in humans, basal cell carcinoma and squamous cell carcinoma.

The team introduced genes in their experiments that cause cancer formation and that induce cells to enter a state of senescence. They found that when CSDE1 was depleted, the cells did not senesce and instead became immortalized, which is a critical pathway to cancer.

Further experiments showed that malignant tumors begin to form after CSDE1-depleted cells are implanted in the skin of mice. The researchers were able to discover this alarming phenomenon because each mouse that received the implant developed squamous cell carcinoma within 15 to 20 days, highlighting the importance of CSDE1 in tumor suppression.

Upon further study, they found that CSDE1 promotes tumor suppression through two distinct mechanisms. cSDE1 induces cells to secrete a mixture of cytokines and enzymes that force the cells into a permanent state of growth arrest. In addition, CSDE1 blocks the synthesis of YBX1, a protein known to promote tumor growth and aggressiveness (https://www.creative-biolabs.com/Membrane-Protein-Service.html).

The findings of this study are surprising, according to the authors, because CSDE1 has previously been linked to increasing cancer growth rather than reducing it. "UNR/CSDE1 Drives a Post-transcriptional Program to Promote Melanoma Invasion and Metastasis", a 2016 study led by Dr. Gebauer, discovered that CSDE1 stimulates the production of metastases in melanoma, a less frequent but more dangerous form of skin cancer. CSDE1 has also been linked to tumor proliferation in a variety of cancers, according to recent research.

"CSDE1 is like a protein with a 'dual personality' with unpredictable dual properties, depending on the type of cell and tissue it is in," explained Dr. Gebauer. "We do not know why this protein promotes cancer in some cases and suppresses it in others. Exploring the underlying causes of this phenomenon will be important for discovering new and more personalized cancer treatments."

CSDE1 is an RNA-binding protein (https://www.creative-biolabs.com/yeast-three-hybrid-y3h-service.html) that normally has the potential to alter its function at the time the RNA is made. One theory that could potentially explain the different expression of CSDE1 is that normal skin cells or tumor cells each have slightly different variants of the protein that affect a wide range of molecular mechanisms in different ways.

The research is one of the few to look at the role of RNA-binding proteins in cellular senescence, which is an exciting new area of cancer research. "RNA-binding proteins have long been thought to be molecules that cells use to regulate basic metabolic tasks and not therapeutic targets. However, this is not the case, and this new sector is crucial for understanding human disease." Dr. Gebauer concluded.

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