Abstract 5336: Macrophage migration inhibitory factor (MIF) plays roles in proliferation, survival and migration of Ewing tumor cells through the activation of several tyrosine kinases

In normal cells, expression of cytokines and their mediated cell signaling pathways are tightly and accurately regulated. But in many tumors, it has been shown that cytokine signaling pathways are deregulated. Thus, identification and understanding of deregulated cytokines and their related pathways can provide the unique and promising opportunity for better-targeted therapies of cancer. MIF has been known to be a proinflammatory cytokine but recently it was shown that MIF plays roles in proliferation, survival and apoptosis in several tumors. In order to study the effects and molecular mechanisms of MIF on Ewing tumor cell growth and survival we established MIF deficient Ewing tumor cell lines using shRNA method. In our study it was found that the decreased MIF expression is significantly correlated to morphological change, deregulation of differentiation, decrease of proliferation and increase of apoptosis in Ewing tumor cells. Then several signal pathways were investigated to elucidate the molecular mechanism of MIF functions in Ewing tumor cells. It has been found that MIF is involved in the activation of Jak/Stat and Src pathways that regulate activation of Akt and Erk, which play key roles in the cell survival and proliferation. Related to the morphological change and mobility change in MIF-deficient cells it was found that Rac1 activation is highly regulated by MIF in Ewing tumors. In addition, it was found that activation of several kinases is closely related to the expression of MIF in Ewing tumors. Therefore our data implies that MIF might functionally contribute to Ewing tumor cell growth, survival, proliferation and metastasis, which suggests that MIF might be a promising target of Ewing tumor cells therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5336. doi:10.1158/1538-7445.AM2011-5336