CD99 triggering induces a novel processes of death in Ewing's sarcoma cells involving reactivation of p53 functions and RAS upregulation.

ABSTRACT: CD99 is a transmembrane protein, whose expression is constantly associated to EwingM-bM-^@M-^Ys Sarcoma (EWS), a class of pediatric bone tumors with particular poor prognosis. We previously reported that engagement of CD99 leads to massive and rapid EWS cell death through a non-canonical path. Here we report that death occurs through a novel mechanism starting from classical apoptotic features, such as phosphatydilserine exposure on cell surface and mitochondrial depolarization and ending with massive cytoplasmic hypervacuolization (autophagosomes and micropinosomes). Mechanistically, CD99 induces upregulation of IGFI-R and RAS and rapid MDM2 degradation, which leads to p53 reactivation. We propose that upon CD99 engagement and subsequent p53 reactivation, the EWS-ets oncogene becomes insu

ORGANISM(S): Homo sapiens

SUBMITTER: Andrea Grilli 

PROVIDER: E-GEOD-36097 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress