IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms12348.html
   My bibliography  Save this article

Cutaneous wound healing through paradoxical MAPK activation by BRAF inhibitors

Author

Listed:
  • Helena Escuin-Ordinas

    (University of California, Los Angeles (UCLA))

  • Shuoran Li

    (University of California, Los Angeles (UCLA))

  • Michael W. Xie

    (University of California, Los Angeles (UCLA))

  • Lu Sun

    (University of California, Los Angeles (UCLA))

  • Willy Hugo

    (University of California, Los Angeles (UCLA))

  • Rong Rong Huang

    (University of California, Los Angeles (UCLA))

  • Jing Jiao

    (University of California, Los Angeles (UCLA)
    University of California, Los Angeles (UCLA))

  • Felipe Meira de-Faria

    (University of California, Los Angeles (UCLA)
    Institute of Biology, University of Campinas – UNICAMP)

  • Susan Realegeno

    (Immunology & Molecular Genetics, University of California, Los Angeles (UCLA))

  • Paige Krystofinski

    (University of California, Los Angeles (UCLA))

  • Ariel Azhdam

    (University of California, Los Angeles (UCLA))

  • Sara Marie D. Komenan

    (Division of Surgical Oncology, Department of Surgery)

  • Mohammad Atefi

    (University of California, Los Angeles (UCLA))

  • Begoña Comin-Anduix

    (Division of Surgical Oncology, Department of Surgery
    Jonsson Comprehensive Cancer Center)

  • Matteo Pellegrini

    (Cell, and Developmental Biology, University of California, Los Angeles (UCLA))

  • Alistair J. Cochran

    (University of California, Los Angeles (UCLA))

  • Robert L. Modlin

    (University of California, Los Angeles (UCLA)
    Jonsson Comprehensive Cancer Center)

  • Harvey R. Herschman

    (University of California, Los Angeles (UCLA)
    University of California, Los Angeles (UCLA)
    Jonsson Comprehensive Cancer Center)

  • Roger S. Lo

    (University of California, Los Angeles (UCLA)
    University of California, Los Angeles (UCLA)
    Jonsson Comprehensive Cancer Center)

  • William H. McBride

    (University of California, Los Angeles (UCLA)
    Division of Surgical Oncology, Department of Surgery)

  • Tatiana Segura

    (University of California, Los Angeles (UCLA))

  • Antoni Ribas

    (University of California, Los Angeles (UCLA)
    University of California, Los Angeles (UCLA)
    Division of Surgical Oncology, Department of Surgery
    Jonsson Comprehensive Cancer Center)

Abstract

BRAF inhibitors are highly effective therapies for the treatment of BRAFV600-mutated melanoma, with the main toxicity being a variety of hyperproliferative skin conditions due to paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway in BRAF wild-type cells. Most of these hyperproliferative skin changes improve when a MEK inhibitor is co-administered, as it blocks paradoxical MAPK activation. Here we show how the BRAF inhibitor vemurafenib accelerates skin wound healing by inducing the proliferation and migration of human keratinocytes through extracellular signal-regulated kinase (ERK) phosphorylation and cell cycle progression. Topical treatment with vemurafenib in two wound-healing mice models accelerates cutaneous wound healing through paradoxical MAPK activation; addition of a mitogen-activated protein kinase kinase (MEK) inhibitor reverses the benefit of vemurafenib-accelerated wound healing. The same dosing regimen of topical BRAF inhibitor does not increase the incidence of cutaneous squamous cell carcinomas in mice. Therefore, topical BRAF inhibitors may have clinical applications in accelerating the healing of skin wounds.

Suggested Citation

  • Helena Escuin-Ordinas & Shuoran Li & Michael W. Xie & Lu Sun & Willy Hugo & Rong Rong Huang & Jing Jiao & Felipe Meira de-Faria & Susan Realegeno & Paige Krystofinski & Ariel Azhdam & Sara Marie D. Ko, 2016. "Cutaneous wound healing through paradoxical MAPK activation by BRAF inhibitors," Nature Communications, Nature, vol. 7(1), pages 1-10, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12348
    DOI: 10.1038/ncomms12348
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms12348
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms12348?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:7:y:2016:i:1:d:10.1038_ncomms12348. 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.