Molecular mechanisms and functions of guanylate-binding protein 2 in inflammation and cancer (Review).

The present review article aimed to summarize currently available research data on the roles and functions of human guanylate-binding protein 2 (hGBP2) and murine (m)GBP2 in cancer and inflammation. In addition, its structure, hydrolytic mechanisms and molecular regulatory mechanisms are discussed. hGBP2 and mGBP2 are strongly induced by IFN-γ through the IFN-sensitive response element and IFN-γ activation site sequences on their corresponding genes, whilst also being regulated by IFN-α, IFN-β and multiple STAT-IFN-regulatory factor complexes. In inflammation, hGBP2 primarily regulates activation of the NLR family pyrin domain-containing 3 and absent in melanoma 2 inflammasome pathways and therefore the induction of pyroptosis. By contrast, in cancer, hGBP2 serves a dual role, such that it can either promote cancer progression or suppress cancer development in a context-dependent manner. This leads to variations in the hGBP2 expression profile across different cancer types in addition to their corresponding prognostic outcomes. hGBP2 can also respond to paclitaxel, a notable anticancer drug. The present review aims to summarize the structural basis and regulatory mechanisms of hGBP2, elucidate the roles of both hGBP2 and mGBP2 in inflammation and cancer and propose prospective research directions to inform future fundamental investigations and clinical applications.