Keratinocytes, the most frequent type of skin cell in the epidermis, were collected from mice by researchers led by Fátima Gebauer at the Centre for Genomic Regulation (CRG). Keratinocytes can cause a variety of skin malignancies, including basal and squamous cell carcinomas, which are two of the most common types of cancer in humans.
Skin Cells From The First Defense Layer Against Cancer
The skin is an appropriate organ system to research tissue and whole-organism responses to local and systemic disturbances because of its accessibility. An increasing body of evidence suggests that the skin plays an important role in immunology, both during tissue homeostasis and in various pathological situations.
The original SALT concept proposed separate circuiting immune cells that constantly travel in a directed manner between the epidermis, draining lymph nodes, and the circulation, enabling optimal immunosurveillance.
Intracellular sensors in the inflammasome complex in keratinocytes are activated as a result of skin exposure to haptens or high amounts of UV irradiation, leading to caspase 1 activation and the processing and secretion of important pro-inflammatory cytokines. As a result, tissue-resident immune cells become activated, inducing and perpetuating an inflammatory response.
CSDE1 enhances tumor suppression through two separate pathways, according to the study. When CSDE1 is triggered, the cell secretes a cocktail of cytokines and enzymes, which causes the cell to go into a persistent growth arrest. CSDE1 also inhibits the synthesis of YBX1, a protein that has been linked to tumor growth and aggressiveness in the past.
The findings of the study are surprising, according to the authors, because CSDE1 has traditionally been related to cancer growth rather than suppression. CSDE1 stimulates the production of metastases in melanoma, the least frequent but most aggressive type of skin cancer, according to previous research done by Dr. Gebauer’s lab. CSDE1 has been associated with tumor proliferation in a variety of cancers in other investigations.
CSDE1 is an RNA-binding protein, a sort of protein that monitors RNA as soon as it’s generated and has the ability to affect its function dramatically. One idea for why CSDE1 behaves differently is that normal skin cells and tumors have slightly different versions of the protein, each of which affects the molecular machinery in distinct ways. Research in this area of cancer research is one of the few to examine the role of RNA-binding proteins in cell senescence, a novel, and exciting development.
As the body’s principal interaction with the environment, the skin serves as the first line of defense against microbial pathogens as well as physical and chemical irritants. Immune sentinels and effector cells have distinct hurdles when it comes to immune surveillance of such a huge and exposed organ. Overwhelming infections or tumors may result if the immune response is insufficient, while chronic inflammation and autoimmunity may develop if the immune response is excessive.
Controlling the scope of an immune response is thus a fundamental problem for preserving skin integrity, which is critical for the survival of the host. To establish immunological homeostasis, the host employs both active defense mechanisms and tolerogenic pathways, ensuring that immune responses in the skin are appropriately adjusted to varied stressors.
Researchers introduced cancer-causing genes into cells, causing the cells to go into dormancy. They discovered that when CSDE1 levels were low, cells were unable to undergo senescence and became immortalized, which is a critical step in the progression of cancer.
Further research confirmed that malignant tumors develop when cells depleted of the CSDE1 protein are placed beneath the skin of mice. The researchers were surprised since every treated mouse developed squamous cell carcinomas within 15 to 20 days, demonstrating the relevance of CSDE1 in tumor suppression.
