Loftus, Alexander E P and Romano, Marianna S and Phuong, Anh Nguyen and McKinnel, Ben J and Muir, Morwenna T and Furqan, Muhammad and Dawson, John C and Avalle, Lidia and Douglas, Adam T and Mort, Richard L and Byron, Adam and Carragher, Neil O and Pollard, Steven M and Brunton, Valerie G and Frame, Margaret C (2024) An ILK/STAT3 pathway controls glioblastoma stem cell plasticity. Developmental Cell. ISSN 1534-5807 (In Press)
Full text not available from this repository.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.