SC-08 * TRANSCRIPTIONAL AND POST-TRANSLATIONAL REGULATIONS OF c-Myc IN GLIOBLASTOMA STEM CELLS
Year: 2014
Type: conference-abstract
Abstract: Glioblastomas are highly lethal brain tumors containing glioma stem cells (GSCs) that display stem cell-like properties. The molecular link between stemness and malignancy in GSCs is not fully understood. c-Myc appears to be the dominant driver linking self-renewal to neoplasia, but how c-Myc is regulated in GSCs is not defined. We previously demonstrated that the zinc finger and X-linked transcription factor (ZFX) controls c-Myc expression to maintain GSC self-renewal and tumorigenic potential. Down-regulation of ZFX by shRNA reduced c-Myc expression and potently inhibited GSC self-renewal and tumor growth in vivo. Ectopic expression of c-Myc to its endogenous level rescued the phenotype caused by ZFX disruption, demonstrating that ZFX controls c-Myc expression to maintain GSC properties. Here we show a post-translational regulation of c-Myc by deubiquitylation in GSCs. Deubiquitylation of c-Myc in GSCs stabilizes c-Myc protein to promote the maintenance of the GSC phenotype. Blocking c-Myc deubiquitylation disrupted GSC self-renewal and tumorigenic potential. These data indicated that c-Myc is regulated at both transcriptional and post-translational levels in GSCs and c-Myc is a dominant driver linking self-renewal to malignancy.
Source: Neuro-Oncology
Institution: Cleveland Clinic
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2320259646