Figure 6.

Effects of CD99 triggering by antibodies in Ewing sarcoma cells. CD99 engagement reduces the malignancy of tumor cells and induces caspase-independent cell death. The antibody-mediated engagement of CD99 induces a rapid caveolin-1-dependent endocytosis and promotes the upregulation of IGF1R and RAS signaling. The activation of the two downstream effectors Rac1 and ERK1/2 leads to macropinocytosis and death by methuosis or neural differentiation, respectively [59,96]. The effects are more dramatic in malignant cells that express high levels of CD99 and are facilitated by the reactivation of P53, resulting from the CD99-induced degradation of MDM2 [51,52,53,92]. Moreover, CD99 ligation upregulates zyxin that is associated with actin filaments and cell aggregation, a process also required for cell death [52].