Numbl Inhibits Glioma Cell Migration and Invasion by Suppressing TRAF5-mediated NF-κB Activation

Overview

Journal Mol Biol Cell

Specialties Cell Biology
Molecular Biology

Date 2012 May 18

PMID 22593207

Citations 42

Authors

Tao Tao

Chun Cheng

Yuhong Ji

Guangfei Xu

Jianguo Zhang

Li Zhang

Aiguo Shen

Affiliations

Soon will be listed here.

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.

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