Bifulco Carlo, McDaniel Katy, Leng Lin, Bucala Richard
Department of Medicine, Pathology, Epidemiology and Public Health, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06520-8031, USA.
Curr Pharm Des. 2008;14(36):3790-801. doi: 10.2174/138161208786898608.
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.
巨噬细胞移动抑制因子（MIF）是一种高度保守且在进化上古老的介质，具有多效性作用，与肿瘤生长和进展有关。MIF的功能在细胞因子中是独特的，其作用延伸到肿瘤发生的多个基本过程，如肿瘤增殖、凋亡逃避、血管生成和侵袭。这些多效性功能方面与MIF独特的信号特性并行，后者涉及ERK-1/2和AKT途径的激活以及JAB1、p53、SCF泛素连接酶和HIF-1的调节。这些特性反映了生长调节、凋亡和细胞周期控制的核心特征，这比免疫细胞因子更为典型。这些促肿瘤特性的重要性在多种癌症的体外和体内模型中以及MIF产生与多种人类肿瘤的肿瘤侵袭性和转移潜能之间的正相关中得到了支持。
