Posts Tagged ‘TNFR-4’

Feeling the Heat – the Link between Inflammation and Cancer

Reporter: Irina Robu, PhD

Researchers at Lerner Research Institute led by Dr. Xiaoxia Li revealed a new signaling pathway in a subset of hair follicle stem cells that can be linked to inflammation, wound healing and tumorigenesis giving new insights into how to potential target to slow or prevent tumor initiation. However, previous research shows that uncontrolled tissue repair is usually associated with tumor formation, but there is no direct connection between them.

The scientists found that the proinflammatory cytokine, IL-17A plays a vital role in aberrant tissue repair. They showed that when IL-17A signaling is turned on, Lrig1+ stem cells expanded and their progeny translocated to other layers of the skin in reply to injury. Through a series of investigations, Dr. Li showed that the presence and physical proximity of a series of proteins sets into motion a complex signaling cascade that results in activation of ERK5 (extracellular signal regulated kinase 5), which is ultimately responsible for the expansion and migration of Lrig1+ stem cells. While many proteins including interleukin-17 receptor, epidermal growth factor receptor and Act1 are involved, tumor necrosis factor receptor associated factor 4 is the first receptor to fail, setting the entire signaling cascade in motion.

Considering that this is the first study to show that a proinflammatory cytokine can recruit a growth factor receptor to activate stem cells in support of tissue repair and tumorigenesis. This proves that tumor necrosis factor receptor associated factor 4 may be a viable therapeutic target to pursue in upcoming studies.



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