IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-11020-3.html
   My bibliography  Save this article

Uncovering the signaling landscape controlling breast cancer cell migration identifies novel metastasis driver genes

Author

Listed:
  • Esmee Koedoot

    (LACDR, Leiden University)

  • Michiel Fokkelman

    (LACDR, Leiden University)

  • Vasiliki-Maria Rogkoti

    (LACDR, Leiden University)

  • Marcel Smid

    (Erasmus University Medical Center)

  • Iris Sandt

    (LACDR, Leiden University)

  • Hans Bont

    (LACDR, Leiden University)

  • Chantal Pont

    (LACDR, Leiden University)

  • Janna E. Klip

    (LACDR, Leiden University)

  • Steven Wink

    (LACDR, Leiden University)

  • Mieke A. Timmermans

    (Erasmus University Medical Center)

  • Erik A. C. Wiemer

    (Erasmus University Medical Center)

  • Peter Stoilov

    (West Virginia University)

  • John A. Foekens

    (Erasmus University Medical Center)

  • Sylvia E. Dévédec

    (LACDR, Leiden University)

  • John W. M. Martens

    (Erasmus University Medical Center)

  • Bob Water

    (LACDR, Leiden University)

Abstract

Ttriple-negative breast cancer (TNBC) is an aggressive and highly metastatic breast cancer subtype. Enhanced TNBC cell motility is a prerequisite of TNBC cell dissemination. Here, we apply an imaging-based RNAi phenotypic cell migration screen using two highly motile TNBC cell lines (Hs578T and MDA-MB-231) to provide a repository of signaling determinants that functionally drive TNBC cell motility. We have screened ~4,200 target genes individually and discovered 133 and 113 migratory modulators of Hs578T and MDA-MB-231, respectively, which are linked to signaling networks predictive for breast cancer progression. The splicing factors PRPF4B and BUD31 and the transcription factor BPTF are essential for cancer cell migration, amplified in human primary breast tumors and associated with metastasis-free survival. Depletion of PRPF4B, BUD31 and BPTF causes primarily down regulation of genes involved in focal adhesion and ECM-interaction pathways. PRPF4B is essential for TNBC metastasis formation in vivo, making PRPF4B a candidate for further drug development.

Suggested Citation

  • Esmee Koedoot & Michiel Fokkelman & Vasiliki-Maria Rogkoti & Marcel Smid & Iris Sandt & Hans Bont & Chantal Pont & Janna E. Klip & Steven Wink & Mieke A. Timmermans & Erik A. C. Wiemer & Peter Stoilov, 2019. "Uncovering the signaling landscape controlling breast cancer cell migration identifies novel metastasis driver genes," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11020-3
    DOI: 10.1038/s41467-019-11020-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-11020-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-11020-3?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Zixiang Wang & Shourong Wang & Junchao Qin & Xiyu Zhang & Gang Lu & Hongbin Liu & Haiyang Guo & Ligang Wu & Victoria O. Shender & Changshun Shao & Beihua Kong & Zhaojian Liu, 2022. "Splicing factor BUD31 promotes ovarian cancer progression through sustaining the expression of anti-apoptotic BCL2L12," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Guidantonio Malagoli Tagliazucchi & Anna J. Wiecek & Eloise Withnell & Maria Secrier, 2023. "Genomic and microenvironmental heterogeneity shaping epithelial-to-mesenchymal trajectories in cancer," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

    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:10:y:2019:i:1:d:10.1038_s41467-019-11020-3. 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.