| First Author | Friedmann-Morvinski D | Year | 2016 |
| Journal | Sci Adv | Volume | 2 |
| Issue | 1 | Pages | e1501292 |
| PubMed ID | 26824076 | Mgi Jnum | J:258176 |
| Mgi Id | MGI:6142480 | Doi | 10.1126/sciadv.1501292 |
| Citation | Friedmann-Morvinski D, et al. (2016) Targeting NF-kappaB in glioblastoma: A therapeutic approach. Sci Adv 2(1):e1501292 |
| abstractText | Glioblastoma multiforme (GBM) is the most common and lethal form of intracranial tumor. We have established a lentivirus-induced mouse model of malignant gliomas, which faithfully captures the pathophysiology and molecular signature of mesenchymal human GBM. RNA-Seq analysis of these tumors revealed high nuclear factor kappaB (NF-kappaB) activation showing enrichment of known NF-kappaB target genes. Inhibition of NF-kappaB by either depletion of IkappaB kinase 2 (IKK2), expression of a IkappaBalphaM super repressor, or using a NEMO (NF-kappaB essential modifier)-binding domain (NBD) peptide in tumor-derived cell lines attenuated tumor proliferation and prolonged mouse survival. Timp1, one of the NF-kappaB target genes significantly up-regulated in GBM, was identified to play a role in tumor proliferation and growth. Inhibition of NF-kappaB activity or silencing of Timp1 resulted in slower tumor growth in both mouse and human GBM models. Our results suggest that inhibition of NF-kappaB activity or targeting of inducible NF-kappaB genes is an attractive therapeutic approach for GBM. |
