How skin cells form the first line of defense against cancer

"We found that the protein CSDE1 orchestrates a complex chain of events to age skin cells," said first author of the study, Rosario Avolio, a postdoctoral researcher at CRG, in presentation of the study.
Significantly slowed their function without causing death
.

" "The resulting cells act as a firewall against cancer, inhibiting tumor formation

The researchers, led by Fátima Gebauer of the Center for Genome Regulation (CRG), carried out the study by collecting keratinocytes, the most abundant skin cell type in the epidermis, from mice
.

Keratinocytes can cause various types of skin cancer, including basal cell carcinoma and squamous cell carcinoma, the two most common types of all human cancers

In their experiments, the team introduced genes that cause cancer to form, thereby inducing cells to enter a state of senescence
.

They found that when levels of CSDE1 were depleted, cells did not senesce but became immortal, a necessary step in cancer development

Further experiments showed that when Csde1-depleted cells were implanted under the skin of mice, they began to form malignant tumors
.

The authors found this to be surprising because each treated mouse developed squamous cell carcinoma within 15 to 20 days, highlighting the importance of CSDE1 in tumor suppression

The researchers found that CSDE1 promotes tumor suppression through two distinct mechanisms
.

CSDE1 induces cells to secrete a cocktail of cytokines and enzymes that force cells into a state of permanent growth arrest

According to the authors, the study's results were surprising because CSDE1 was previously thought to be involved in cancer formation, rather than suppressing it
.

Previous research by the same research group, led by Dr.

"CSDE1 is the 'Dr incarnation' of the protein world
.

It has an unpredictable dual nature, depending on what type of cell and tissue it is found in," explains Dr.

CSDE1, an RNA-binding protein, is a protein that monitors RNA, often after it is made, with the potential to significantly change its function
.

One theory that might explain the different behavior of CSDE1 is that normal skin cells or tumor cells have slightly different variants of the protein that affect broader molecular mechanisms in different ways

The study is one of a handful to investigate the role of RNA-binding proteins in establishing cellular senescence, an important new frontier in cancer research
.
RNA-binding proteins have long been thought to be general-purpose molecules that cells use for general housework, and that they cannot be targeted for therapy
.
But this is not the case, and this emerging field is critical to understanding human disease
.
” concluded Dr.
Gebauer
.

Journal Reference :

1. Rosario Avolio, Marta Inglés-Ferrándiz, Annagiulia Ciocia, Olga Coll, Sarah Bonnin, Tanit Guitart, Anna Ribó, Fátima Gebauer.
   Coordinated post-transcriptional control of oncogene-induced senescence by UNR/CSDE1 .
   Cell Reports , 2022; 38 (2): 110211 DOI: 10.
   1016/j.
   celrep.
   2021.
   110211