TMIC-44. TARGETING BRACHYURY REPROGRAMS ENDOTHELIAL TRANSDIFFERENTIATION OF GLIOBLASTOMA

Abstract Glioblastoma (GBM) is the most common and aggressive primary brain tumor with a median survival of only 15 months 5-year less than 5% despite best available treatments. Tumor recurrence/progression therapy resistance are major obstacles for GBM treatment. characterized by intensive vascular proliferation that associated cell growth, invasion, to chemo/radiotherapy, decreased disease-free survival. Increasing data have shown existence cells endothelial characteristics called derived cells, which come from transdifferentiation and, more specifically, stem (GSCs). However, molecular mechanisms underlying this process remain largely unknown. GSCs tightly regulated distinct transcriptional programs driven nuclear transcription factors. Brachyury factor expressed in normal, undifferentiated embryonic notochord axial skeleton plays an important role development differentiation during normal development. Here, we show brachyury highly patient-derived cells. Functional studies demonstrate fibroblast growth receptor 1 (FGFR1)/mitogen-activated protein kinase (MAPK). Our further disclose FGFR1/MAPK-directed activation promotes GSC formation via 2 (VEGFR2), whereas pharmacological inhibition FGFR1 MAPK or shRNA-mediated downregulation decreases into suppresses stemness VEGFR2. findings highlight importance FGFR1/MAPK-regulated VEGFR2, targeting FGFR1-MAPK-brachyury-VEGFR2 signal pathway may represent novel therapeutic strategy reprogramming driving progression.