Warburg Effect Metabolism Drives Neoplasia in a Drosophila Genetic Model of Epithelial Cancer

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Warburg Effect Metabolism Drives Neoplasia in a Drosophila Genetic Model of Epithelial Cancer. / Eichenlaub, Teresa; Villadsen, René; Freitas, Flávia C.P.; Andrejeva, Diana; Aldana, Blanca I.; Nguyen, Hung Than; Petersen, Ole William; Gorodkin, Jan; Herranz, Héctor; Cohen, Stephen M.

In: Current Biology, Vol. 28, No. 20, 2018, p. 3220-3228.e6.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Eichenlaub, T, Villadsen, R, Freitas, FCP, Andrejeva, D, Aldana, BI, Nguyen, HT, Petersen, OW, Gorodkin, J, Herranz, H & Cohen, SM 2018, 'Warburg Effect Metabolism Drives Neoplasia in a Drosophila Genetic Model of Epithelial Cancer', Current Biology, vol. 28, no. 20, pp. 3220-3228.e6. https://doi.org/10.1016/j.cub.2018.08.035

APA

Eichenlaub, T., Villadsen, R., Freitas, F. C. P., Andrejeva, D., Aldana, B. I., Nguyen, H. T., ... Cohen, S. M. (2018). Warburg Effect Metabolism Drives Neoplasia in a Drosophila Genetic Model of Epithelial Cancer. Current Biology, 28(20), 3220-3228.e6. https://doi.org/10.1016/j.cub.2018.08.035

Vancouver

Eichenlaub T, Villadsen R, Freitas FCP, Andrejeva D, Aldana BI, Nguyen HT et al. Warburg Effect Metabolism Drives Neoplasia in a Drosophila Genetic Model of Epithelial Cancer. Current Biology. 2018;28(20):3220-3228.e6. https://doi.org/10.1016/j.cub.2018.08.035

Author

Eichenlaub, Teresa ; Villadsen, René ; Freitas, Flávia C.P. ; Andrejeva, Diana ; Aldana, Blanca I. ; Nguyen, Hung Than ; Petersen, Ole William ; Gorodkin, Jan ; Herranz, Héctor ; Cohen, Stephen M. / Warburg Effect Metabolism Drives Neoplasia in a Drosophila Genetic Model of Epithelial Cancer. In: Current Biology. 2018 ; Vol. 28, No. 20. pp. 3220-3228.e6.

Bibtex

@article{4b5334a9dcb84fcc9fe041ac420d2f49,
title = "Warburg Effect Metabolism Drives Neoplasia in a Drosophila Genetic Model of Epithelial Cancer",
abstract = "Cancers develop in a complex mutational landscape. Genetic models of tumor formation have been used to explore how combinations of mutations cooperate to promote tumor formation in vivo. Here, we identify lactate dehydrogenase (LDH), a key enzyme in Warburg effect metabolism, as a cooperating factor that is both necessary and sufficient for epidermal growth factor receptor (EGFR)-driven epithelial neoplasia and metastasis in a Drosophila model. LDH is upregulated during the transition from hyperplasia to neoplasia, and neoplasia is prevented by LDH depletion. Elevated LDH is sufficient to drive this transition. Notably, genetic alterations that increase glucose flux, or a high-sugar diet, are also sufficient to promote EGFR-driven neoplasia, and this depends on LDH activity. We provide evidence that increased LDHA expression promotes a transformed phenotype in a human primary breast cell culture model. Furthermore, analysis of publically available cancer data showed evidence of synergy between elevated EGFR and LDHA activity linked to poor clinical outcome in a number of human cancers. Altered metabolism has generally been assumed to be an enabling feature that accelerates cancer cell proliferation. Our findings provide evidence that sugar metabolism may have a more profound role in driving neoplasia than previously appreciated. Eichenlaub et al. examine gene expression changes during the transition from hyperplasia to neoplasia and identify lactate dehydrogenase as a key driver of neoplasia in a Drosophila EGFR model. Elevated sugar flux or a high-sugar diet also drive neoplasia. Synergy between EGFR and LDHA correlates with poor clinical outcome in some human cancers.",
keywords = "cancer, lactate dehydrogenase, metabolism, Warburg effect",
author = "Teresa Eichenlaub and Ren{\'e} Villadsen and Freitas, {Fl{\'a}via C.P.} and Diana Andrejeva and Aldana, {Blanca I.} and Nguyen, {Hung Than} and Petersen, {Ole William} and Jan Gorodkin and H{\'e}ctor Herranz and Cohen, {Stephen M.}",
year = "2018",
doi = "10.1016/j.cub.2018.08.035",
language = "English",
volume = "28",
pages = "3220--3228.e6",
journal = "Current Biology",
issn = "0960-9822",
publisher = "Cell Press",
number = "20",

}

RIS

TY - JOUR

T1 - Warburg Effect Metabolism Drives Neoplasia in a Drosophila Genetic Model of Epithelial Cancer

AU - Eichenlaub, Teresa

AU - Villadsen, René

AU - Freitas, Flávia C.P.

AU - Andrejeva, Diana

AU - Aldana, Blanca I.

AU - Nguyen, Hung Than

AU - Petersen, Ole William

AU - Gorodkin, Jan

AU - Herranz, Héctor

AU - Cohen, Stephen M.

PY - 2018

Y1 - 2018

N2 - Cancers develop in a complex mutational landscape. Genetic models of tumor formation have been used to explore how combinations of mutations cooperate to promote tumor formation in vivo. Here, we identify lactate dehydrogenase (LDH), a key enzyme in Warburg effect metabolism, as a cooperating factor that is both necessary and sufficient for epidermal growth factor receptor (EGFR)-driven epithelial neoplasia and metastasis in a Drosophila model. LDH is upregulated during the transition from hyperplasia to neoplasia, and neoplasia is prevented by LDH depletion. Elevated LDH is sufficient to drive this transition. Notably, genetic alterations that increase glucose flux, or a high-sugar diet, are also sufficient to promote EGFR-driven neoplasia, and this depends on LDH activity. We provide evidence that increased LDHA expression promotes a transformed phenotype in a human primary breast cell culture model. Furthermore, analysis of publically available cancer data showed evidence of synergy between elevated EGFR and LDHA activity linked to poor clinical outcome in a number of human cancers. Altered metabolism has generally been assumed to be an enabling feature that accelerates cancer cell proliferation. Our findings provide evidence that sugar metabolism may have a more profound role in driving neoplasia than previously appreciated. Eichenlaub et al. examine gene expression changes during the transition from hyperplasia to neoplasia and identify lactate dehydrogenase as a key driver of neoplasia in a Drosophila EGFR model. Elevated sugar flux or a high-sugar diet also drive neoplasia. Synergy between EGFR and LDHA correlates with poor clinical outcome in some human cancers.

AB - Cancers develop in a complex mutational landscape. Genetic models of tumor formation have been used to explore how combinations of mutations cooperate to promote tumor formation in vivo. Here, we identify lactate dehydrogenase (LDH), a key enzyme in Warburg effect metabolism, as a cooperating factor that is both necessary and sufficient for epidermal growth factor receptor (EGFR)-driven epithelial neoplasia and metastasis in a Drosophila model. LDH is upregulated during the transition from hyperplasia to neoplasia, and neoplasia is prevented by LDH depletion. Elevated LDH is sufficient to drive this transition. Notably, genetic alterations that increase glucose flux, or a high-sugar diet, are also sufficient to promote EGFR-driven neoplasia, and this depends on LDH activity. We provide evidence that increased LDHA expression promotes a transformed phenotype in a human primary breast cell culture model. Furthermore, analysis of publically available cancer data showed evidence of synergy between elevated EGFR and LDHA activity linked to poor clinical outcome in a number of human cancers. Altered metabolism has generally been assumed to be an enabling feature that accelerates cancer cell proliferation. Our findings provide evidence that sugar metabolism may have a more profound role in driving neoplasia than previously appreciated. Eichenlaub et al. examine gene expression changes during the transition from hyperplasia to neoplasia and identify lactate dehydrogenase as a key driver of neoplasia in a Drosophila EGFR model. Elevated sugar flux or a high-sugar diet also drive neoplasia. Synergy between EGFR and LDHA correlates with poor clinical outcome in some human cancers.

KW - cancer

KW - lactate dehydrogenase

KW - metabolism

KW - Warburg effect

U2 - 10.1016/j.cub.2018.08.035

DO - 10.1016/j.cub.2018.08.035

M3 - Journal article

VL - 28

SP - 3220-3228.e6

JO - Current Biology

JF - Current Biology

SN - 0960-9822

IS - 20

ER -

ID: 209060214