IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-27451-w.html
   My bibliography  Save this article

Nuclear pore protein NUP210 depletion suppresses metastasis through heterochromatin-mediated disruption of tumor cell mechanical response

Author

Listed:
  • Ruhul Amin

    (NIH)

  • Anjali Shukla

    (NIH)

  • Jacqueline Jufen Zhu

    (The Jackson Laboratory for Genomic Medicine)

  • Sohyoung Kim

    (NIH)

  • Ping Wang

    (The Jackson Laboratory for Genomic Medicine)

  • Simon Zhongyuan Tian

    (The Jackson Laboratory for Genomic Medicine)

  • Andy D. Tran

    (NIH
    NIH)

  • Debasish Paul

    (NIH)

  • Steven D. Cappell

    (NIH)

  • Sandra Burkett

    (NIH)

  • Huaitian Liu

    (NIH
    NIH)

  • Maxwell P. Lee

    (NIH
    NIH)

  • Michael J. Kruhlak

    (NIH
    NIH)

  • Jennifer E. Dwyer

    (NIH)

  • R. Mark Simpson

    (NIH)

  • Gordon L. Hager

    (NIH)

  • Yijun Ruan

    (The Jackson Laboratory for Genomic Medicine)

  • Kent W. Hunter

    (NIH)

Abstract

Mechanical signals from the extracellular microenvironment have been implicated in tumor and metastatic progression. Here, we identify nucleoporin NUP210 as a metastasis susceptibility gene for human estrogen receptor positive (ER+) breast cancer and a cellular mechanosensor. Nup210 depletion suppresses lung metastasis in mouse models of breast cancer. Mechanistically, NUP210 interacts with LINC complex protein SUN2 which connects the nucleus to the cytoskeleton. In addition, the NUP210/SUN2 complex interacts with chromatin via the short isoform of BRD4 and histone H3.1/H3.2 at the nuclear periphery. In Nup210 knockout cells, mechanosensitive genes accumulate H3K27me3 heterochromatin modification, mediated by the polycomb repressive complex 2 and differentially reposition within the nucleus. Transcriptional repression in Nup210 knockout cells results in defective mechanotransduction and focal adhesion necessary for their metastatic capacity. Our study provides an important role of nuclear pore protein in cellular mechanosensation and metastasis.

Suggested Citation

  • Ruhul Amin & Anjali Shukla & Jacqueline Jufen Zhu & Sohyoung Kim & Ping Wang & Simon Zhongyuan Tian & Andy D. Tran & Debasish Paul & Steven D. Cappell & Sandra Burkett & Huaitian Liu & Maxwell P. Lee , 2021. "Nuclear pore protein NUP210 depletion suppresses metastasis through heterochromatin-mediated disruption of tumor cell mechanical response," Nature Communications, Nature, vol. 12(1), pages 1-23, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27451-w
    DOI: 10.1038/s41467-021-27451-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-27451-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-27451-w?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:12:y:2021:i:1:d:10.1038_s41467-021-27451-w. 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.