LSD1 Performs Demethylase-Independent and Context-Specific Roles in Ewing Sarcoma.

ABSTRACT: Lysine specific demethylase 1 (LSD1), encoded by the gene KDM1A, is overexpressed and correlates with poor patient prognosis in Ewing sarcoma. LSD1 and the pathognomonic fusion oncoprotein, EWSR1::FLI1, colocalize throughout the genome, suggesting LSD1 is a critical co-regulator driving the progression of Ewing sarcoma. However, therapeutic targeting of LSD1 by competitive and noncompetitive inhibitors has yielded mixed results. Irreversible, enzymatic inhibition seems ineffective, but reversible noncompetitive inhibition has predominant off target mechanisms, leaving open the question of LSD1 function in Ewing sarcoma. Here we take a robust approach through multiple methods of depletion in multiple EwS cell lines to define enzymatic and nonenzymatic contributions of LSD1 to transcr

SUBMITTER: Dreher RD 

PROVIDER: S-EPMC12710800 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature