1. Cell Biology
  2. Chromosomes and Gene Expression
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ATM regulation of IL-8 links oxidative stress to cancer cell migration and invasion

  1. Wei-Ta Chen
  2. Nancy D Ebelt
  3. Travis H Stracker
  4. Blerta Xhemalce
  5. Carla L Van Den Berg
  6. Kyle M Miller  Is a corresponding author
  1. University of Texas at Austin, United States
  2. Institute for Research in Biomedicine, Spain
Research Article
  • Cited 35
  • Views 3,564
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Cite this article as: eLife 2015;4:e07270 doi: 10.7554/eLife.07270

Abstract

Ataxia-telangiectasia mutated (ATM) protein kinase regulates the DNA damage response (DDR) and is associated with cancer suppression. Here we report a cancer-promoting role for ATM. ATM depletion in metastatic cancer cells reduced cell migration and invasion. Transcription analyses identified a gene network, including the chemokine IL-8, regulated by ATM. IL-8 expression required ATM and was regulated by oxidative stress. IL-8 was validated as an ATM target by its ability to rescue cell migration and invasion defects in ATM-depleted cells. Finally, ATM-depletion in human breast cancer cells reduced lung tumors in a mouse xenograft model and clinical data validated IL-8 in lung metastasis. These findings provide insights into how ATM activation by oxidative stress regulates IL-8 to sustain cell migration and invasion in cancer cells to promote metastatic potential. Thus, in addition to well-established roles in tumor suppression, these findings identify a role for ATM in tumor progression.

Article and author information

Author details

  1. Wei-Ta Chen

    Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Nancy D Ebelt

    Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Travis H Stracker

    Oncology Programme, Institute for Research in Biomedicine, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  4. Blerta Xhemalce

    Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Carla L Van Den Berg

    Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Kyle M Miller

    Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, United States
    For correspondence
    kyle.miller@austin.utexas.edu
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: Experiments involving Balb/c mice for this study were performed in strict accordance with guidelines set forth for the handling and care of animals by the institutional animal care and use committee (IACUC) protocols (AUP-2012-00075) of the University of Texas at Austin.

Reviewing Editor

  1. Joaquin M Espinosa, University of Colorado Boulder, United States

Publication history

  1. Received: February 28, 2015
  2. Accepted: May 31, 2015
  3. Accepted Manuscript published: June 1, 2015 (version 1)
  4. Version of Record published: June 12, 2015 (version 2)

Copyright

© 2015, Chen 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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