Looking in the miR-ror: TGF-β–mediated activation of NF-κB in glioma
Christine E. Eyler, Jeremy N. Rich
Christine E. Eyler, Jeremy N. Rich
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Commentary

Looking in the miR-ror: TGF-β–mediated activation of NF-κB in glioma

Abstract

The explosive growth in our understanding of the molecular underpinnings of glioblastomas has served as an instructive paradigm for other cancers. However, the exact nature by which many of the pathogenic drivers connect is less well known, and elucidation of relationships between critical genetic and signaling alterations may inform the development of therapeutic approaches to the disease. In this issue, Song et al. identify miR-182 induction as a mechanism by which TGF-β stimulation aberrantly activates NF-κB signaling in glioblastoma cells, clarifying a critical point of cross-talk between molecular signaling pathways. Their findings provide a greater understanding of the complex interplay between signaling pathways in cancer that may ultimately prove useful in the development of synergistic targeting approaches.

Authors

Christine E. Eyler, Jeremy N. Rich

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Figure 1

Effects of TGF-β signaling in glioblastoma.

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Effects of TGF-β signaling in glioblastoma. TGF-β signaling is dysregula...
TGF-β signaling is dysregulated on several levels in cancers, including glioblastoma, and mediates many systemic (immunosuppressive and angiogenic) and cellular effects. In contrast to other cancers, the canonical TGF-β pathway (ligand receptor/Smad mediators) is not commonly mutated in glioblastomas. However, modifiers of TGF-β signaling (e.g., FOXO, FOXG1, BF1, and USP15) and interaction with other pathways lead to a shift from primarily tumor-suppressive effects (e.g., antiproliferation) to oncogenesis. Targeting the interactions between TGF-β and NF-κB signaling may offer therapeutic options. Amplification of EGFR, an NF-κB activator, and mutation of NFKBIA (a NF-κB inhibitor) are mutually exclusive and may inform the effects of two miRs that regulate NF-κB activity, miR-182 and miR-30e*. The role of TGF-β and its relationship to other signaling pathways in gliomas contradicts the growth-suppressive effects and alternative signaling effects of TGF-β in noncancerous cells, such as astrocytes.