scholarly journals Antagonism of the mammalian target of rapamycin selectively mediates metabolic effects of epidermal growth factor receptor inhibition and protects human malignant glioma cells from hypoxia-induced cell death

Brain ◽  
2009 ◽  
Vol 132 (6) ◽  
pp. 1509-1522 ◽  
Author(s):  
Michael W. Ronellenfitsch ◽  
Daniel P. Brucker ◽  
Michael C. Burger ◽  
Stefan Wolking ◽  
Felix Tritschler ◽  
...  
Keyword(s):  
Cell Death ◽  
Epidermal Growth Factor Receptor ◽  
Mammalian Target Of Rapamycin ◽  
Growth Factor Receptor ◽  
Glioma Cells ◽  
Metabolic Effects ◽  
Receptor Inhibition ◽  
Human Malignant Glioma ◽  
Epidermal Growth ◽  
Malignant Glioma Cells

scholarly journals Activation of Epidermal Growth Factor Receptor Sensitizes Glioblastoma Cells to Hypoxia-Induced Cell Death

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2144
Author(s):  
Anna-Luisa Luger ◽  
Nadja I. Lorenz ◽  
Hans Urban ◽  
Iris Divé ◽  
Anna L. Engel ◽  
...  
Keyword(s):  
Cell Death ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Atp Depletion ◽  
Metabolic Effects ◽  
Metabolic Adaptation ◽  
Egfr Activation ◽  
Epidermal Growth

Background: The epidermal growth factor receptor (EGFR) signaling pathway is genetically activated in approximately 50% of glioblastomas (GBs). Its inhibition has been explored clinically but produced disappointing results, potentially due to metabolic effects that protect GB cells against nutrient deprivation and hypoxia. Here, we hypothesized that EGFR activation could disable metabolic adaptation and define a GB cell population sensitive to starvation. Methods: Using genetically engineered GB cells to model different types of EGFR activation, we analyzed changes in metabolism and cell survival under conditions of the tumor microenvironment. Results: We found that expression of mutant EGFRvIII as well as EGF stimulation of EGFR-overexpressing cells impaired physiological adaptation to starvation and rendered cells sensitive to hypoxia-induced cell death. This was preceded by adenosine triphosphate (ATP) depletion and an increase in glycolysis. Furthermore, EGFRvIII mutant cells had higher levels of mitochondrial superoxides potentially due to decreased metabolic flux into the serine synthesis pathway which was associated with a decrease in the NADPH/NADP+ ratio. Conclusions: The finding that EGFR activation renders GB cells susceptible to starvation could help to identify a subgroup of patients more likely to benefit from starvation-inducing therapies.

scholarly journals Activation of AMP-activated kinase modulates sensitivity of glioma cells against epidermal growth factor receptor inhibition

2016 ◽  
Vol 49 (1) ◽  
pp. 173-180 ◽  
Author(s):  
INES HARTEL ◽  
MICHAEL RONELLENFITSCH ◽  
CHRISTINA WANKA ◽  
STEFAN WOLKING ◽  
JOACHIM P. STEINBACH ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Glioma Cells ◽  
Receptor Inhibition ◽  
Epidermal Growth
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