YAP1 is a key regulator of EWS::FLI1-dependent malignant transformation upon IGF-1-mediated reprogramming of bone mesenchymal stem cells.

ABSTRACT: Ewing sarcoma (EwS) is an aggressive cancer of adolescents in need of effective treatment. Insulin-like growth factor (IGF)-1 is an autocrine growth factor for EwS, but only 10% of patients respond to IGF-1 receptor (IGF-1R) blockade. Although EwS is presumed to originate from mesenchymal progenitors during bone development, targeting of the EwS driver oncogene EWS::FLI1 to the mesenchymal lineage in a mouse model does not result in tumor formation but in skeletal malformations and perinatal death. We report that transient exposure to IGF-1 concentrations mimicking serum levels during puberty reprograms limb-derived mesenchymal cells of EWS::FLI1-mutant mice to stable transformation and tumorigenicity. We identify a modular mechanism of IGF-1-driven tumor promotion in the early steps of Ew

SUBMITTER: Noorizadeh R 

PROVIDER: S-EPMC11936874 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature