title: Numbl inhibits glioma cell migration and invasion by suppressing TRAF5-mediated NF-κB activation.
abstract: The Notch signaling regulator Numblike (Numbl) is expressed in the brain, but little is known regarding its role in the pathophysiology of glial cells. In this paper, we report that Numbl expression was down-regulated in high-grade human glioma tissue samples and glioblastoma cell lines. To investigate the role of Numbl in glioma migration and invasion, we generated human glioma cell lines in which Numbl was either overexpressed or depleted. Overexpression of Numbl suppressed, while elimination of Numbl promoted, the migration and invasion of glioma cells. Numbl inhibited glioma migration and invasion by dampening NF-κB activity. Furthermore, Numbl interacted directly with tumor necrosis factor receptor-associated factor 5 (TRAF5), which signals upstream and is required for the activation of NF-κB, and committed it to proteasomal degradation by promoting K48-linked polyubiquitination of TRAF5. In conclusion, our data suggest that Numbl negative regulates glioma cell migration and invasion by abrogating TRAF5-induced activation of NF-κB.
authors.affiliation: Key Laboratory of Neuroregeneration of Jiangsu Province, Nantong University, Nantong, Jiangsu, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tao
authors.forename: Chun
authors.initials: C
authors.lastname: Cheng
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Ji
authors.forename: Guangfei
authors.initials: G
authors.lastname: Xu
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Aiguo
authors.initials: A
authors.lastname: Shen
mesh_terms: D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D048015:TNF Receptor-Associated Factor 5 / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; C530266:NUMBL protein, human; D048015:TNF Receptor-Associated Factor 5