MIF family proteins in genitourinary cancer: tumorigenic roles and therapeutic potential

Genitourinary cancers encompass some of the most common solid tumours and have high rates of morbidity and mortality. Inflammation is associated with enhanced tumorigenesis, and a number of pro-inflammatory mediators, such as macrophage migration inhibitory factor (MIF), also promote tumorigenesis. Studies of the role of MIF (which largely functions via the type II transmembrane receptor CD74) in prostate, bladder and kidney cancers suggest that it is a pro-tumorigenic factor in genitourinary malignancy. Inhibiting MIF activity in cell culture and in preclinical animal models of genitourinary cancers reduces the phenotypic hallmarks of cancer, such as proliferation, angiogenesis and tumour aggressiveness, by downregulating signalling pathways such as those regulated by extracellular signal-regulated kinase (ERK), protein kinase B and p53, and MIF may also reverse immunosuppression. Progress has been made in our understanding of the role of MIF (and its family member d-dopachrome tautomerase (DDT)) in genitourinary cancers and how it can be therapeutically targeted. Macrophage migration inhibitory factor (MIF) can promote tumorigenesis by acting directly on cancer cells and by reversing immunosuppression. Advances have been made in our understanding of the role of MIF in the promotion of, and as a treatment target for, genitourinary cancers.