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.
Original language | English |
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Article number | e7 |
Pages (from-to) | 3197-3212 |
Journal | Developmental cell |
Volume | 59 |
Issue number | 24 |
Early online date | 25 Sept 2024 |
DOIs | |
Publication status | Published - 16 Dec 2024 |
Keywords
- cancer
- glioblastoma
- adhesion
- integrin-linked kinase
- plasticity
- stem cells
- astrocytes
- STAT3