Immunology research update from www.immunopaedia.org.za
In a recent paper from Cell Reports researchers have highlighted brought to light, new insights into the molecular mechanisms that dictate our body’s natural ability to defend itself against skin cancer. These insights may open the door for improved therapeutics and targets for the treatment of the disease.
Avolio, et al., reported that the protein CSDE1 coordinates a complex chain of events that enable senescence in skin cells, significantly slowing down their function without causing death. The result, cells that acting like a wall to protect one against cancer, further suppressing the formation of tumours.
Through collection of keratinocytes from mice, the most abundant type of skin cell in the epidermis, the researchers were able to investigate their hypothesis. Interestingly, keratinocytes can give rise to various types of skin cancer including basal and squamous cell carcinomas, the most common form of cancers in humans.
Through induction of cell senescence by promoting cancer growth within the cells through manipulation of certain genes, they reported a reduced level of CSDE1. This led to cells becoming immortalised, an essential step in cancer progression.
When CSDE1 was reduced in cells and implanted under the skin of mice, they started forming malignant tumours. Additionally, they discovered that CSDE1 promotes tumour suppression via two different mechanisms. CSDE1 promotes cytokine expression and enzyme production in the cell, forcing a state of growth arrest. It also stops the synthesis of YBX1, a protein known to promote tumour cell proliferation.
What was interesting is that previously CSDE1 was linked to driving the formation of cancers and did not suppressing them. CSDE1 is an RNA-binding protein, a type of protein that regulates RNA synthesis and translation.
This is a relatively novel study, investigating RNA-binding proteins and how they establish cell senescence which offers major insights into our understanding of cancer.
Journal article: Avolio, R., et al., 2022. Coordinated post-transcriptional control of oncogene-induced senescence by UNR/CSDE1. Cell Reports.