KLF6 depletion promotes NF-κB signaling in glioblastoma.
Oncogene 2017 Jun 22; 36(25):3562-3575
Dysregulation of the NF-κB transcription factor occurs in many cancer types. Krüppel-like family of transcription factors (KLFs) regulate the expression of genes involved in cell proliferation, differentiation and survival. Here, we report a new mechanism of NF-κB activation in glioblastoma through depletion of the KLF6 tumor suppressor. We show that KLF6 transactivates multiple genes negatively controlling the NF-κB pathway and consequently reduces NF-κB nuclear localization and downregulates NF-κB targets. Reconstitution of KLF6 attenuates their malignant phenotype and induces neural-like differentiation and senescence, consistent with NF-κB pathway inhibition. KLF6 is heterozygously deleted in 74.5% of the analyzed glioblastomas and predicts unfavorable patient prognosis suggesting that haploinsufficiency is a clinically relevant means of evading KLF6-dependent regulation of NF-κB. Together, our study identifies a new mechanism by which KLF6 regulates NF-κB signaling, and how this mechanism is circumvented in glioblastoma through KLF6 loss. Oncogene 2017 Jun 22; 36(25):3562-3575.
Masilamani, A P; Ferrarese, R; Kling, E; Thudi, N K; Kim, Hoon; Scholtens, D M; Dai, F; Hadler, M; Unterkircher, T; Platania, L; Weyerbrock, A; Prinz, M; Gillespie, G Y; Harsh Iv, G R; Bredel, M; and Carro, M S, "KLF6 depletion promotes NF-κB signaling in glioblastoma." (2017). Faculty Research 2017. 129.