what is the real correlation between migration inhibitory factor (MIF) and Cancer ?
Macrophage migration inhibitory factor (MIF) is one of the first cytokine mediators. MIF activity correlated with delayed-type hypersensitivity in vitro, and it engendered substantial interest from immunologists because it represented a soluble factor that could be manipulated experimentally. The MIF-binding receptor was identified recently by expression cloning as CD74 , which is the cell-surface form of the MHC class II invariant chain. The absence of motifs for second-messenger activation within the short intracytoplasmic domain of CD74 then led to studies establishing that signal transduction requires the recruitment and activation of an additional protein, CD44.. With regard to signal transduction, MIF has the unusual ability to stimulate sustained ERK1 and ERK2 MAP kinase activation, which is a feature of transformation by oncogenic Ras mutations. MIF also has been shown to antagonize the growth arrest and pro-apoptotic actions of the tumor suppressor p53 , which is induced in normal cells to limit excessive pro-inflammatory responses. MIF's unique spectrum of activity thus may explain not only its central role in innate immunity but also long-standing observations regarding the important role of persistent or recurrent inflammation in cancer development.
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