Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

Serine/Threonine Kinase MLK4 Determines Mesenchymal Identity in Glioma Stem Cells in an NF-kappaB-dependent Manner.

Kim S.H., Ezhilarasan R., Phillips E., Gallego-Perez D., Sparks A., Taylor D., Ladner K., Furuta T., Sabit H., Chhipa R., Cho J.H., Mohyeldin A., Beck S., Kurozumi K., Kuroiwa T., Iwata R., Asai A., Kim J., Sulman E.P., Cheng S.Y., Lee L.J., Nakada M., Guttridge D., DasGupta B., Goidts V., Bhat K.P., Nakano I.

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.

Cancer Cell 29:201-213(2016) [PubMed] [Europe PMC]

UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again