In vivo genetic dissection of tumor growth and the warburg effect

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Abstract

A well-characterized metabolic landmark for aggressive cancers is the reprogramming from oxidative phosphorylation to aerobic glycolysis, referred to as the Warburg effect. Models mimicking this process are often incomplete due to genetic complexities of tumors and cell lines containing unmapped collaborating mutations. In order to establish a system where individual components of oncogenic signals and metabolic pathways can be readily elucidated, we induced a glycolytic tumor in the Drosophila wing imaginal disc by activating the oncogene PDGF/VEGF-receptor (Pvr). This causes activation of multiple oncogenic pathways including Ras, PI3K/Akt, Raf/ERK, Src and JNK. Together this network of genes stabilizes Hifα (Sima) that in turn, transcriptionally up-regulates many genes encoding glycolytic enzymes. Collectively, this network of genes also causes inhibition of pyruvate dehydrogenase (PDH) activity resulting in diminished ox-phos levels. The high ROS produced during this process functions as a feedback signal to consolidate this metabolic reprogramming.

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Cheng-Wei Wang

Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Arunima Purkayastha

Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Kevin T Jones

Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Shivani K Thaker

Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Utpal Banerjee

Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States

For correspondence
banerjee@mbi.ucla.edu

Competing interests
Utpal Banerjee, Reviewing editor, eLife.

"This ORCID iD identifies the author of this article:" 0000-0001-6247-0284

Funding

American Cancer Society (Postdoctoral fellowship (#PF-10-130-01-DDC))

Kevin T Jones

National Institutes of Health (RO1-EY008152)

Utpal Banerjee

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.