The unfolded protein response sensor PERK mediates mechanical stress-induced maturation of focal adhesion complexes in glioblastoma cells.

Autor: Khoonkari M; Department of Medical Oncology, University of Groningen, University Medical Center Groningen, The Netherlands.; Zernike Institute for Advanced Materials, University of Groningen, The Netherlands., Liang D; Department of Medical Oncology, University of Groningen, University Medical Center Groningen, The Netherlands., Kamperman M; Zernike Institute for Advanced Materials, University of Groningen, The Netherlands., van Rijn P; Department of Biomedical Engineering-FB40, University of Groningen, University Medical Center Groningen, The Netherlands.; W.J. Kolff Institute for Biomedical Engineering and Materials Science-FB41, University of Groningen, University Medical Center Groningen, The Netherlands., Kruyt FAE; Department of Medical Oncology, University of Groningen, University Medical Center Groningen, The Netherlands.
Jazyk: angličtina
Zdroj: FEBS letters [FEBS Lett] 2024 Dec; Vol. 598 (24), pp. 3021-3035. Date of Electronic Publication: 2024 Aug 16.
DOI: 10.1002/1873-3468.14996
Abstrakt: Stiffening of the brain extracellular matrix (ECM) in glioblastoma promotes tumor progression. Previously, we discovered that protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) plays a role in glioblastoma stem cell (GSC) adaptation to matrix stiffness through PERK/FLNA-dependent F-actin remodeling. Here, we examined the involvement of PERK in detecting stiffness changes via focal adhesion complex (FAC) formation. Compared to control GSCs, PERK-deficient GSCs show decreased vinculin and tensin expression, while talin and integrin-β1 remain constant. Furthermore, vimentin was also reduced while tubulin increased, and a stiffness-dependent increase of the differentiation marker GFAP expression was absent in PERK-deficient GSCs. In conclusion, our study reveals a novel role for PERK in FAC formation during matrix stiffening, which is likely linked to its regulation of F-actin remodeling.
(© 2024 The Author(s). FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
Databáze: MEDLINE
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