Human Brat Ortholog TRIM3 Is a Tumor Suppressor That Regulates Asymmetric Cell Division in Glioblastoma

摘要: Cancer stem cells, capable of self-renewal and multipotent differentiation, influence tumor behavior through a complex balance symmetric asymmetric cell divisions. Mechanisms regulating the dynamics cells their progeny in human cancer are poorly understood. In Drosophila, mutation brain (brat) leads to loss normal division by developing neural results massively enlarged composed neuroblasts with neoplastic properties. Brat promotes directs differentiation at least partially its suppression on Myc. We identified TRIM3 (11p15.5) as ortholog Drosophila brat demonstrate regulation properties glioblastoma (GBM), highly malignant tumor. gene expression is markedly reduced GBM samples, neurosphere cultures, lines reconstitution impairs growth vitro vivo. attenuates stem-like qualities primary including formation markers CD133, Nestin, Nanog. greater percentage dividing asymmetrically rather than symmetrically. As suppresses c-Myc activity glioma lines. also strong Musashi–Notch signaling neurospheres that may better explain effect dynamics. conclude acts suppressor restoring division. Res; 74(16); 4536–48. ©2014 AACR.