Journal article
Glutathione peroxidase 4 overexpression induces anomalous subdiffusion and impairs glioblastoma cell growth
Journal of biological engineering, Vol.18(1), 72
12/21/2024
DOI: 10.1186/s13036-024-00472-x
PMCID: PMC11663334
PMID: 39709480
Abstract
Glioblastoma tumors are the most common and aggressive adult central nervous system malignancy. Nearly all patients experience disease progression, which significantly contributes to disease mortality. Recently, it has been suggested that recurrent tumors may be characterized by a ferroptosis-prone phenotype with a significant decrease in glutathione peroxidase 4 (GPx4) expression. This led to the hypothesis that GPx4 expression negatively influences GBM cell growth. This study utilizes a doxycycline inducible GPx4 overexpression model to test this hypothesis. Consistently, the overexpression of GPx4 significantly impairs cell growth and colony formation while also causing an accumulation of cells in G1/G0 phase of the cell cycle. From a biophysical perspective, GPx4 overexpressing cells have significantly greater surface area, increased Young's modulus, and experience anomalous sub-diffusion as opposed to normal diffusion associated with Brownian motion. Moreover, analysis of patient derived GBM cells reveal that cell growth rates, plating efficiency, and Young's modulus are all inversely proportional to GPx4 expression. Therefore, GPx4 appears to be a biophysical regulator of GBM cell growth that warrants further mechanistic investigation in its role in GBM progression.Glioblastoma tumors are the most common and aggressive adult central nervous system malignancy. Nearly all patients experience disease progression, which significantly contributes to disease mortality. Recently, it has been suggested that recurrent tumors may be characterized by a ferroptosis-prone phenotype with a significant decrease in glutathione peroxidase 4 (GPx4) expression. This led to the hypothesis that GPx4 expression negatively influences GBM cell growth. This study utilizes a doxycycline inducible GPx4 overexpression model to test this hypothesis. Consistently, the overexpression of GPx4 significantly impairs cell growth and colony formation while also causing an accumulation of cells in G1/G0 phase of the cell cycle. From a biophysical perspective, GPx4 overexpressing cells have significantly greater surface area, increased Young's modulus, and experience anomalous sub-diffusion as opposed to normal diffusion associated with Brownian motion. Moreover, analysis of patient derived GBM cells reveal that cell growth rates, plating efficiency, and Young's modulus are all inversely proportional to GPx4 expression. Therefore, GPx4 appears to be a biophysical regulator of GBM cell growth that warrants further mechanistic investigation in its role in GBM progression.
Details
- Title: Subtitle
- Glutathione peroxidase 4 overexpression induces anomalous subdiffusion and impairs glioblastoma cell growth
- Creators
- Nahom Teferi - University of IowaAkalanka Ekanayake - University of IowaStephenson B Owusu - University of IowaThomas O Moninger - University of IowaJann N Sarkaria - Mayo Clinic in ArizonaAlexei V Tivanski - University of IowaMichael S Petronek - University of Iowa, Radiation Oncology
- Resource Type
- Journal article
- Publication Details
- Journal of biological engineering, Vol.18(1), 72
- DOI
- 10.1186/s13036-024-00472-x
- PMID
- 39709480
- PMCID
- PMC11663334
- NLM abbreviation
- J Biol Eng
- ISSN
- 1754-1611
- eISSN
- 1754-1611
- Publisher
- BMC
- Grant note
- National Institutes of HealthUniversity of Iowa Central Microscopy, Radiation and Free Radical
The content is solely the responsibility of the authors and does not represent the views of the National Institutes of Health. We would like to acknowledge the University of Iowa Central Microscopy, Radiation and Free Radical, and Flow Cytometry core facilities for their support of this work.
- Language
- English
- Date published
- 12/21/2024
- Academic Unit
- Iowa Neuroscience Institute; Radiation Oncology; Radiation Research Laboratory; Chemistry
- Record Identifier
- 9984758182902771
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