1. Serine/Threonine Kinase MLK4 Determines Mesenchymal Identity in Glioma Stem Cells in an NF-κB-dependent Manner.
- Author
-
Kim, Sung-Hak, Ezhilarasan, Ravesanker, Phillips, Emma, Gallego-Perez, Daniel, Sparks, Amanda, Taylor, David, Ladner, Katherine, Furuta, Takuya, Sabit, Hemragul, Chhipa, Rishi, Cho, Ju Hwan, Mohyeldin, Ahmed, Beck, Samuel, Kurozumi, Kazuhiko, Kuroiwa, Toshihiko, Iwata, Ryoichi, Asai, Akio, Kim, Jonghwan, Sulman, Erik P., and Cheng, Shi-Yuan
- Subjects
- *
SERINE/THREONINE kinases , *MESENCHYMAL stem cells , *GLIOMAS , *STEM cells , *NF-kappa B - Abstract
Summary Activation of nuclear factor κB (NF-κB) induces mesenchymal (MES) transdifferentiation and radioresistance in glioma stem cells (GSCs), but molecular mechanisms for NF-κB activation in GSCs are currently unknown. Here, we report that mixed lineage kinase 4 (MLK4) is overexpressed in MES but not proneural (PN) GSCs. Silencing MLK4 suppresses self-renewal, motility, tumorigenesis, and radioresistance of MES GSCs via a loss of the MES signature. MLK4 binds and phosphorylates the NF-κB regulator IKKα, leading to activation of NF-κB signaling in GSCs. MLK4 expression is inversely correlated with patient prognosis in MES, but not PN high-grade gliomas. Collectively, our results uncover MLK4 as an upstream regulator of NF-κB signaling and a potential molecular target for the MES subtype of glioblastomas. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF