1. Cancer Biology
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Essential roles of Caspase-3 in facilitating Myc-induced genetic instability and carcinogenesis

  1. Ian M Cartwright
  2. Xinjian Liu
  3. Min Zhou
  4. Fang Li
  5. Chuan-Yuan Li  Is a corresponding author
  1. University of Colorado School of Medicine, United States
  2. Duke University Medical Center, United States
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Cite this article as: eLife 2017;6:e26371 doi: 10.7554/eLife.26371

Abstract

The mechanism for Myc-induced genetic instability is not well understood. Here we show that sublethal activation of Caspase-3 plays an essential, facilitative role in Myc-induced genomic instability and oncogenic transformation. Overexpression of Myc resulted in increased numbers of chromosome aberrations and γH2AX foci in non-transformed MCF10A human mammary epithelial cells. However, such increases were almost completely eliminated in isogenic cells with CASP3 gene ablation. Furthermore, we show that endonuclease G, an apoptotic nuclease downstream of Caspase-3, is directly responsible Myc-induced genetic instability. Genetic ablation of either CASP3 or ENDOG prevented Myc-induced oncogenic transformation of MCF10A cells. Taken together, we believe that Caspase-3 plays a critical, unexpected role in mediating Myc-induced genetic instability and transformation in mammalian cells.

Article and author information

Author details

  1. Ian M Cartwright

    Department of Urology, University of Colorado School of Medicine, Aurora, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Xinjian Liu

    Department of Dermatology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Min Zhou

    Department of Dermatology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Fang Li

    Department of Dermatology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Chuan-Yuan Li

    Department of Dermatology, Duke University Medical Center, Durham, United States
    For correspondence
    chuan.li@duke.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0418-6231

Funding

National Cancer Institute (CA155720)

  • Chuan-Yuan Li

National Institute of Environmental Health Sciences (ES024015)

  • Chuan-Yuan Li

National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR066527)

  • Chuan-Yuan Li

National Cancer Institute (2008852)

  • Chuan-Yuan Li

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

Ethics

Animal experimentation: The animal experiments conducted in this study were approved by the Duke University Institutional Animal Use and Care Committee (IACUC) with the protocol number A195-14-98.

Reviewing Editor

  1. Chi Van Dang, University of Pennsylvania, United States

Publication history

  1. Received: February 27, 2017
  2. Accepted: July 7, 2017
  3. Accepted Manuscript published: July 10, 2017 (version 1)
  4. Version of Record published: August 9, 2017 (version 2)

Copyright

© 2017, Cartwright 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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