KLF6 depletion promotes NF-κB signaling in glioblastoma

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

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Oncogene. - 36, 25 (2017) , 3562-3575, ISSN: 1476-5594

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2019
• Urheber: Masilamani, Anie P. ; Ferrarese, Roberto ; Kling, Eva ; Thudi, N. K. ; Kim, Hoon ; Scholtens, Denise M. ; Dai, Fangping ; Hadler, Michael ; Unterkircher, Thomas ; Platania, Leonardo ; Weyerbrock, Astrid ; Prinz, Marco ; Gillespie, George Yancey ; Harsh, Griffith R. ; Bredel, Markus ; Carro, Maria Stella
• Beteiligte Personen und Organisationen: Klinik für Neurochirurgie. Freiburg im Breisgau ; Institut für Neuropathologie. Freiburg im Breisgau

Weitere Informationen

• DOI: 10.1038/onc.2016.507
• URN: urn:nbn:de:bsz:25-freidok-1369393
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 25.03.2025, 13:51 MEZ