IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-09711-y.html
   My bibliography  Save this article

LNK suppresses interferon signaling in melanoma

Author

Listed:
  • Ling-Wen Ding

    (Cancer Science Institute of Singapore, National University of Singapore)

  • Qiao-Yang Sun

    (Cancer Science Institute of Singapore, National University of Singapore)

  • Jarem J. Edwards

    (Melanoma Institute Australia, The University of Sydney
    Sydney Medical School, The University of Sydney)

  • Lucia Torres Fernández

    (Cancer Science Institute of Singapore, National University of Singapore)

  • Xue-Bin Ran

    (Cancer Science Institute of Singapore, National University of Singapore)

  • Si-Qin Zhou

    (Cancer Science Institute of Singapore, National University of Singapore)

  • Richard A. Scolyer

    (Melanoma Institute Australia, The University of Sydney
    Sydney Medical School, The University of Sydney
    Royal Prince Alfred Hospital, Sydney)

  • James S. Wilmott

    (Melanoma Institute Australia, The University of Sydney
    Sydney Medical School, The University of Sydney)

  • John F. Thompson

    (Melanoma Institute Australia, The University of Sydney
    Sydney Medical School, The University of Sydney
    Royal Prince Alfred Hospital, Sydney)

  • Ngan Doan

    (Santa Monica-University of California, Los Angeles Medical Center)

  • Jonathan W. Said

    (Santa Monica-University of California, Los Angeles Medical Center)

  • Nachiyappan Venkatachalam

    (Cancer Science Institute of Singapore, National University of Singapore)

  • Jin-Fen Xiao

    (Cancer Science Institute of Singapore, National University of Singapore)

  • Xin-Yi Loh

    (Cancer Science Institute of Singapore, National University of Singapore)

  • Maren Pein

    (Cancer Science Institute of Singapore, National University of Singapore)

  • Liang Xu

    (Cancer Science Institute of Singapore, National University of Singapore)

  • David W. Mullins

    (Geisel School of Medicine at Dartmouth)

  • Henry Yang

    (Cancer Science Institute of Singapore, National University of Singapore)

  • De-Chen Lin

    (Cedars-Sinai Medical Center, UCLA School of Medicine)

  • H. Phillip Koeffler

    (Cancer Science Institute of Singapore, National University of Singapore
    Cedars-Sinai Medical Center, UCLA School of Medicine)

Abstract

LNK (SH2B3) is a key negative regulator of JAK-STAT signaling which has been extensively studied in malignant hematopoietic diseases. We found that LNK is significantly elevated in cutaneous melanoma; this elevation is correlated with hyperactive signaling of the RAS-RAF-MEK pathway. Elevated LNK enhances cell growth and survival in adverse conditions. Forced expression of LNK inhibits signaling by interferon-STAT1 and suppresses interferon (IFN) induced cell cycle arrest and cell apoptosis. In contrast, silencing LNK expression by either shRNA or CRISPR-Cas9 potentiates the killing effect of IFN. The IFN-LNK signaling is tightly regulated by a negative feedback mechanism; melanoma cells exposed to IFN upregulate expression of LNK to prevent overactivation of this signaling pathway. Our study reveals an unappreciated function of LNK in melanoma and highlights the critical role of the IFN-STAT1-LNK signaling axis in this potentially devastating disease. LNK may be further explored as a potential therapeutic target for melanoma immunotherapy.

Suggested Citation

  • Ling-Wen Ding & Qiao-Yang Sun & Jarem J. Edwards & Lucia Torres Fernández & Xue-Bin Ran & Si-Qin Zhou & Richard A. Scolyer & James S. Wilmott & John F. Thompson & Ngan Doan & Jonathan W. Said & Nachiy, 2019. "LNK suppresses interferon signaling in melanoma," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09711-y
    DOI: 10.1038/s41467-019-09711-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-09711-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-09711-y?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. Chun Wai Wong & Christos Evangelou & Kieran N. Sefton & Rotem Leshem & Wei Zhang & Vishaka Gopalan & Sorayut Chattrakarn & Macarena Lucia Fernandez Carro & Erez Uzuner & Holly Mole & Daniel J. Wilcock, 2023. "PARP14 inhibition restores PD-1 immune checkpoint inhibitor response following IFNγ-driven acquired resistance in preclinical cancer models," Nature Communications, Nature, vol. 14(1), pages 1-21, 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_s41467-019-09711-y. 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.