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,
Ferrarese R,
Kling E,
Thudi N,
Kim H,
Scholtens D,
Dai F,
Hadler M,
Unterkircher T,
Platania L,
Weyerbrock A,
Prinz M,
Gillespie G,
Harsh Iv G,
Bredel M,
Carro M.
KLF6 depletion promotes NF-κB signaling in glioblastoma. Oncogene 2017 Jun 22; 36(25):3562-3575