IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-04572-3.html
   My bibliography  Save this article

In vivo screening identifies GATAD2B as a metastasis driver in KRAS-driven lung cancer

Author

Listed:
  • Caitlin L. Grzeskowiak

    (Baylor College of Medicine)

  • Samrat T. Kundu

    (The University of Texas MD Anderson Cancer Center)

  • Xiulei Mo

    (Emory University School of Medicine)

  • Andrei A. Ivanov

    (Emory University School of Medicine)

  • Oksana Zagorodna

    (Baylor College of Medicine)

  • Hengyu Lu

    (Baylor College of Medicine)

  • Richard H. Chapple

    (Baylor College of Medicine)

  • Yiu Huen Tsang

    (Baylor College of Medicine)

  • Daniela Moreno

    (Baylor College of Medicine)

  • Maribel Mosqueda

    (University of Texas MD Anderson Cancer Center)

  • Karina Eterovic

    (University of Texas MD Anderson Cancer Center)

  • Jared J. Fradette

    (The University of Texas MD Anderson Cancer Center)

  • Sumreen Ahmad

    (The University of Texas MD Anderson Cancer Center)

  • Fengju Chen

    (Baylor College of Medicine)

  • Zechen Chong

    (The University of Texas MD Anderson Cancer Center)

  • Ken Chen

    (The University of Texas MD Anderson Cancer Center)

  • Chad J. Creighton

    (Baylor College of Medicine
    The University of Texas MD Anderson Cancer Center
    Baylor College of Medicine)

  • Haian Fu

    (Emory University School of Medicine)

  • Gordon B. Mills

    (University of Texas MD Anderson Cancer Center)

  • Don L. Gibbons

    (The University of Texas MD Anderson Cancer Center
    University of Texas MD Anderson Cancer Center)

  • Kenneth L. Scott

    (Baylor College of Medicine)

Abstract

Genetic aberrations driving pro-oncogenic and pro-metastatic activity remain an elusive target in the quest of precision oncology. To identify such drivers, we use an animal model of KRAS-mutant lung adenocarcinoma to perform an in vivo functional screen of 217 genetic aberrations selected from lung cancer genomics datasets. We identify 28 genes whose expression promoted tumor metastasis to the lung in mice. We employ two tools for examining the KRAS-dependence of genes identified from our screen: 1) a human lung cell model containing a regulatable mutant KRAS allele and 2) a lentiviral system permitting co-expression of DNA-barcoded cDNAs with Cre recombinase to activate a mutant KRAS allele in the lungs of mice. Mechanistic evaluation of one gene, GATAD2B, illuminates its role as a dual activity gene, promoting both pro-tumorigenic and pro-metastatic activities in KRAS-mutant lung cancer through interaction with c-MYC and hyperactivation of the c-MYC pathway.

Suggested Citation

  • Caitlin L. Grzeskowiak & Samrat T. Kundu & Xiulei Mo & Andrei A. Ivanov & Oksana Zagorodna & Hengyu Lu & Richard H. Chapple & Yiu Huen Tsang & Daniela Moreno & Maribel Mosqueda & Karina Eterovic & Jar, 2018. "In vivo screening identifies GATAD2B as a metastasis driver in KRAS-driven lung cancer," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04572-3
    DOI: 10.1038/s41467-018-04572-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-04572-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-04572-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04572-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.