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

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Activation of Epidermal Growth Factor Receptor Sensitizes Glioblastoma Cells to Hypoxia-Induced Cell Death. / Luger, Anna-Luisa; Lorenz, Nadja I; Urban, Hans; Divé, Iris; Engel, Anna L; Strassheimer, Florian; Dettmer, Katja; Zeiner, Pia S; Shaid, Shabnam; Struve, Nina; Kriegs, Malte; Hofmann, Ute; Oefner, Peter J; Harter, Patrick N; Steinbach, Joachim P; Ronellenfitsch, Michael W.

in: CANCERS, Jahrgang 12, Nr. 8, 03.08.2020.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Luger, A-L, Lorenz, NI, Urban, H, Divé, I, Engel, AL, Strassheimer, F, Dettmer, K, Zeiner, PS, Shaid, S, Struve, N, Kriegs, M, Hofmann, U, Oefner, PJ, Harter, PN, Steinbach, JP & Ronellenfitsch, MW 2020, 'Activation of Epidermal Growth Factor Receptor Sensitizes Glioblastoma Cells to Hypoxia-Induced Cell Death', CANCERS, Jg. 12, Nr. 8. https://doi.org/10.3390/cancers12082144

APA

Luger, A-L., Lorenz, N. I., Urban, H., Divé, I., Engel, A. L., Strassheimer, F., Dettmer, K., Zeiner, P. S., Shaid, S., Struve, N., Kriegs, M., Hofmann, U., Oefner, P. J., Harter, P. N., Steinbach, J. P., & Ronellenfitsch, M. W. (2020). Activation of Epidermal Growth Factor Receptor Sensitizes Glioblastoma Cells to Hypoxia-Induced Cell Death. CANCERS, 12(8). https://doi.org/10.3390/cancers12082144

Vancouver

Luger A-L, Lorenz NI, Urban H, Divé I, Engel AL, Strassheimer F et al. Activation of Epidermal Growth Factor Receptor Sensitizes Glioblastoma Cells to Hypoxia-Induced Cell Death. CANCERS. 2020 Aug 3;12(8). https://doi.org/10.3390/cancers12082144

Bibtex

@article{fcffa0076f25461c8c12d3b88933c8c7,
title = "Activation of Epidermal Growth Factor Receptor Sensitizes Glioblastoma Cells to Hypoxia-Induced Cell Death",
abstract = "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.",
author = "Anna-Luisa Luger and Lorenz, {Nadja I} and Hans Urban and Iris Div{\'e} and Engel, {Anna L} and Florian Strassheimer and Katja Dettmer and Zeiner, {Pia S} and Shabnam Shaid and Nina Struve and Malte Kriegs and Ute Hofmann and Oefner, {Peter J} and Harter, {Patrick N} and Steinbach, {Joachim P} and Ronellenfitsch, {Michael W}",
year = "2020",
month = aug,
day = "3",
doi = "10.3390/cancers12082144",
language = "English",
volume = "12",
journal = "CANCERS",
issn = "2072-6694",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "8",

}

RIS

TY - JOUR

T1 - Activation of Epidermal Growth Factor Receptor Sensitizes Glioblastoma Cells to Hypoxia-Induced Cell Death

AU - Luger, Anna-Luisa

AU - Lorenz, Nadja I

AU - Urban, Hans

AU - Divé, Iris

AU - Engel, Anna L

AU - Strassheimer, Florian

AU - Dettmer, Katja

AU - Zeiner, Pia S

AU - Shaid, Shabnam

AU - Struve, Nina

AU - Kriegs, Malte

AU - Hofmann, Ute

AU - Oefner, Peter J

AU - Harter, Patrick N

AU - Steinbach, Joachim P

AU - Ronellenfitsch, Michael W

PY - 2020/8/3

Y1 - 2020/8/3

N2 - 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.

AB - 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.

U2 - 10.3390/cancers12082144

DO - 10.3390/cancers12082144

M3 - SCORING: Journal article

C2 - 32756332

VL - 12

JO - CANCERS

JF - CANCERS

SN - 2072-6694

IS - 8

ER -