Title
KLF6 depletion promotes NF-κB signaling in glioblastoma.
Document Type
Article
Publication Date
6-22-2017
JAX Source
Oncogene 2017 Jun 22; 36(25):3562-3575
Volume
36
Issue
25
First Page
3562
Last Page
3575
ISSN
1476-5594
PMID
28166199
DOI
https://doi.org/10.1038/onc.2016.507
Abstract
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.
Recommended Citation
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.
https://mouseion.jax.org/stfb2017/129