PLX178165

GSE86518: Genome-wide mRNA expression in human glioblastoma cells and glioblastoma stem cells expressing or not Omomyc

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

MYC deregulation is common in human cancer and has a role in sustaining the aggressive cancer stem cell populations. MYC mediates a broad transcriptional response controlling normal biological programs but its activity is not clearly understood. We address MYC function in cancer stem cells through the inducible expression of Omomyc a MYC derived polypeptide interfering with MYC activity taking as model the most lethal brain tumour, glioblastoma. Omomyc bridles the key cancer stem-like cell features and affects tumour microenvironment, inhibiting angiogenesis. This occurs because Omomyc interferes with proper Myc localisation and binds to DNA, with a preference for sites previously occupied by MYC. This is accompanied by (leads to) selective repression of master transcription factors for glioblastoma stem-like cell identity like POU3F2, SOX2, and OLIG2, upregulation of effectors of tumour suppression and differentiation such as PTEN, ID4, MIAT, and modulation of the expression of microRNAs that target molecules implicated in glioblastoma growth and invasion like EGFR and ZEB1. Data support a novel view of MYC as a network stabiliser that strengthens the regulatory nodes of the gene expression programs controlling cell phenotype and highlight Omomyc as model molecule for targeting cancer stem cells. SOURCE: Federico Zambelli University of Milan