Tumor growth-promoting properties of macrophage migration inhibitory factor.
Macrophage migration inhibitor factor (MIF) is a highly conserved and evolutionarily ancient mediator with pleiotropic effects that has been implicated in tumor growth and progression. MIF's function is unique among cytokines and its effects extend to multiple processes fundamental to tumorigenesis such as tumor proliferation, evasion of apoptosis, angiogenesis and invasion. These pleiotropic functional aspects are paralleled by MIF's unique signaling properties, which involve activation of the ERK-1/2 and AKT pathways and the regulation of JAB1, p53, SCF ubiquitin ligases and HIF-1. These properties reflect features central to growth regulation, apoptosis and cell cycle control than is typical for an immune cytokine. The significance of these pro-tumorigenic properties has found support in several in vitro and in vivo models of cancer and in the positive association between MIF production and tumor aggressiveness and metastatic potential in a variety of human tumors.
Bifulco
Carlo
C
Department of Medicine, Pathology, Epidemiology and Public Health, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06520-8031, USA.
McDaniel
Katy
K
Leng
Lin
L
Bucala
Richard
R
D002455:Cell Division / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000166:cytology; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000098:blood supply / Q000473:pathology*; D009389:Neovascularization, Pathologic; D011487:Protein Conformation; D015398:Signal Transduction
D008263:Macrophage Migration-Inhibitory Factors