In vivo genetic dissection of tumor growth and the warburg effect

  1. Cheng-Wei Wang
  2. Arunima Purkayastha
  3. Kevin T Jones
  4. Shivani K Thaker
  5. Utpal Banerjee  Is a corresponding author
  1. University of California, Los Angeles, United States

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.

Article and author information

Author details

  1. 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.
  2. Arunima Purkayastha

    Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  3. 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.
  4. 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.
  5. 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.
    ORCID icon "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.

Reviewing Editor

  1. K VijayRaghavan, Tata Institute of Fundamental Research, India

Publication history

  1. Received: May 25, 2016
  2. Accepted: August 31, 2016
  3. Accepted Manuscript published: September 1, 2016 (version 1)
  4. Version of Record published: September 20, 2016 (version 2)

Copyright

© 2016, Wang et al.

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.

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  1. Cheng-Wei Wang
  2. Arunima Purkayastha
  3. Kevin T Jones
  4. Shivani K Thaker
  5. Utpal Banerjee
(2016)
In vivo genetic dissection of tumor growth and the warburg effect
eLife 5:e18126.
https://doi.org/10.7554/eLife.18126

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