Year-end Sale % OFF 
Abstract
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.
Highlights
Epithelial-mesenchymal transition (EMT) was first described in the setting of embryonic development as an essential process required for multiple stages of organ and tissue differentiation [1].EMT involves the loss of processes that promote cellular polarity and cell-cell contact and the gain of mesenchymal characteristics, including the ability to migrate and invade [2]
While cancer-associated EMT has primarily been studied in the setting of carcinoma, mesenchymal differentiation is seen in other cancer types, including glioblastoma (GBM) [4]
Activation and CD44 expression were previously shown to occur in GBM stem-like cells (GSCs) in response to TNFα released by infiltrating tumor-associated macrophages and microglia (TAMs) [13], we found that high Bcl-3 augments these responses to further promote mesenchymal change
Summary
Epithelial-mesenchymal transition (EMT) was first described in the setting of embryonic development as an essential process required for multiple stages of organ and tissue differentiation [1]. Like EMT, GBM cells can undergo proneural-mesenchymal-transition (PMT), either spontaneously [12,17] or in response to DNA damaging therapy [4,18,19]. In GBM, unbiased interrogation of gene regulation in mesenchymal tumors demonstrated that they are regulated by specific master transcription factors, including transcriptional coactivator with PDZ-binding motif (TAZ), C/EBPβ and STAT3 [21,22]. Intertwined in this complex mesenchymal transcriptional network reside the nuclear factor-κB (NF-κB) family of proteins. Factors and co-regulators, such as STAT3, Bcl-3 and HIF-1α
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
