A study identifies proteins and mechanisms by which cells defend against skin cancer

Research by researchers at the Centre for Genome Regulation (CRG) of the Barcelona Institute of Science and Technology has revealed important new insights into the molecular mechanisms that underpin the body's natural defenses against the development of skin cancer

"We found that the protein CSDE1 coordinates a complex chain reaction of events that age skin cells and significantly reduce their function without causing death," said Rosario Avolio, Ph.

Oncogenic transformation is a multistep process, but cells can employ antagonism mechanisms as a first line of defense against unrestricted cell proliferation, the authors write

Among other features, senescence includes secretion of a cocktail of cytokines, chemokines, growth factors, and proteases, collectively referred to as the senescence-associated secretory phenotype (SASP)

For their study, CRG researchers and colleagues collected keratinocytes -- the most abundant type of skin cell in the epidermis -- from mice

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

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

"Unbiased multi-omics studies reveal two independent molecular mechanisms by which CSDE1 cooperates to promote senescence, stabilize SASP factor mRNA, and inhibit YBX1 mRNA translation,

The authors say the findings are surprising because CSDE1 was previously thought to be involved in the formation of cancer, rather than suppressing it

"CSDE1 is very much a 'dr

One possible theory to explain how CSDE1 behaves differently 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