NF-κB, Mesenchymal Differentiation and Glioblastoma

Although glioblastoma (GBM) has always been recognized as a heterogeneous tumor, the advent of largescale molecular analysis has enabled robust categorization of this malignancy into several specific subgroups. Among the subtypes designated by expression profiling, mesenchymal tumors have been associated with an inflammatory microenvironment, increased angiogenesis, and resistance to therapy. Nuclear factor-κB (NF-κB) is a ubiquitous transcription factor that plays a prominent role in mediating many of the central features associated with mesenchymal differentiation. This review summarizes the mechanisms by which NF-κB proteins and their co-regulating partners induce the transcriptional network that underlies the mesenchymal phenotype. Moreover, both the intrinsic changes within mesenchymal GBM cells and the microenvironmental factors that modify the overall NF-κB response are detailed.