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Ewing sarcoma (EWS) is an aggressive pediatric bone tumor characterized by unmet clinical needs and an incompletely understood epigenetic heterogeneity. Here, we considered CD99, a major surface molecule hallmark of EWS malignancy. Fluctuations in CD99 expression strongly impair cell dissemination, differentiation, and death. CD99 is also loaded within extracellular vesicles (EVs), and the delivery of CD99-positive or CD99-negative EVs dynamically exerts oncogenic or oncosuppressive functions to recipient cells, respectively. We undertook mass spectrometry and functional annotation analysis to investigate the consequences of CD99 silencing on the proteomic landscape of EWS cells and related EVs. Our data demonstrate that (i) the decrease in CD99 leads to major changes in the proteomic profile of EWS cells and EVs; (ii) intracellular and extracellular compartments display two distinct signatures of differentially expressed proteins; (iii) proteomic changes converge to the modulation of cell migration and immune-modulation biological processes; and (iv) CD99-silenced cells and related EVs are characterized by a migration-suppressive, pro-immunostimulatory proteomic profile. Overall, our data provide a novel source of CD99-associated protein biomarkers to be considered for further validation as mediators of EWS malignancy and as EWS disease liquid biopsy markers. [ABSTRACT FROM AUTHOR]

This document is an editorial published in the journal Frontiers in Cell & Developmental Biology. It discusses the role of RNA-binding proteins (RBPs) in cancer and their potential as therapeutic targets. The editorial highlights recent research on RBPs in cancer, including their involvement in tumor subtyping, response to treatment, and patient survival. The document also mentions specific studies on RBPs in colon and rectal carcinomas, muscle cell differentiation, translation initiation in glioblastoma, and RNA epigenetic modifications in various cancers. Overall, the editorial emphasizes the importance of further research on RBPs and their potential as tools in cancer treatment. [Extracted from the article]