KLF6 depletion promotes NF-κB signaling in glioblastoma

Academic Article


  • 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.
  • Published In

  • Oncogene  Journal
  • Digital Object Identifier (doi)

    Author List

  • Masilamani AP; Ferrarese R; Kling E; Thudi NK; Kim H; Scholtens DM; Dai F; Hadler M; Unterkircher T; Platania L
  • Start Page

  • 3562
  • End Page

  • 3575
  • Volume

  • 36
  • Issue

  • 25