IL-1α Processing, Signaling and Its Role in Cancer Progression

Interleukin-1 alpha (IL-1 alpha) is a major alarmin cytokine which triggers and boosts the inflammatory responses. Since its discovery in the 1940s, the structure and bioactivity of IL-1 alpha has been extensively studied and emerged as a vital regulator in inflammation and hematopoiesis. IL-1 alpha is translated as a pro-form with minor bioactivity. The pro-IL-1 alpha can be cleaved by several proteases to generate the N terminal and C terminal form of IL-1 alpha. The C terminal form of IL-1 alpha (mature form) has several folds higher bioactivity compared with its pro-form. IL-1 alpha is a unique cytokine which could localize in the cytosol, membrane, nucleus, as well as being secreted out of the cell. However, the processing mechanism and physiological significance of these differentially localized IL-1 alpha are still largely unknown. Accumulating evidence suggests IL-1 alpha is involved in cancer pathogenesis. The role of IL-1 alpha in cancer development is controversial as it exerts both pro- and anti-tumor roles in different cancer types. Here, we review the recent development in the processing and signaling of IL-1 alpha and summarize the functions of IL-1 alpha in cancer development.

Automated summary

Interleukin-1 alpha is an important alarmin cytokine that can localize in various cellular compartments and is involved in cancer pathogenesis with both pro- and anti-tumor roles. The processing mechanism and physiological significance of differentially localized IL-1 alpha are still largely unknown, but more research is needed to understand its functions in cancer development.