Home > Research > Publications & Outputs > An ILK/STAT3 pathway controls glioblastoma stem...

Links

Text available via DOI:

View graph of relations

An ILK/STAT3 pathway controls glioblastoma stem cell plasticity

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Published
  • Alexander E P Loftus
  • Marianna S Romano
  • Anh Nguyen Phuong
  • Ben J McKinnel
  • Morwenna T Muir
  • Muhammad Furqan
  • John C Dawson
  • Lidia Avalle
  • Adam T Douglas
  • Richard L Mort
  • Adam Byron
  • Neil O Carragher
  • Steven M Pollard
  • Valerie G Brunton
  • Margaret C Frame
Close
<mark>Journal publication date</mark>16/12/2024
<mark>Journal</mark>Developmental Cell
Issue number24
Volume59
Number of pages16
Pages (from-to)3197-3212.e7
Publication StatusPublished
<mark>Original language</mark>English

Abstract

Glioblastoma (GBM) is driven by malignant neural stem-like cells that display extensive heterogeneity and phenotypic plasticity, which drive tumor progression and therapeutic resistance. Here, we show that the extracellular matrix-cell adhesion protein integrin-linked kinase (ILK) stimulates phenotypic plasticity and mesenchymal-like, invasive behavior in a murine GBM stem cell model. ILK is required for the interconversion of GBM stem cells between malignancy-associated glial-like states, and its loss produces cells that are unresponsive to multiple cell state transition cues. We further show that an ILK/STAT3 signaling pathway controls the plasticity that enables transition of GBM stem cells to an astrocyte-like state in vitro and in vivo. Finally, we find that ILK expression correlates with expression of STAT3-regulated proteins and protein signatures describing astrocyte-like and mesenchymal states in patient tumors. This work identifies ILK as a pivotal regulator of multiple malignancy-associated GBM phenotypes, including phenotypic plasticity and mesenchymal state.

Bibliographic note

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.