IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-23973-5.html
   My bibliography  Save this article

BRN2 is a non-canonical melanoma tumor-suppressor

Author

Listed:
  • Michael Hamm

    (Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Normal and Pathological Development of Melanocytes
    Université Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation radiobiologie et cancer
    Equipes Labellisées Ligue Contre le Cancer)

  • Pierre Sohier

    (Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Normal and Pathological Development of Melanocytes
    Université Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation radiobiologie et cancer
    Equipes Labellisées Ligue Contre le Cancer)

  • Valérie Petit

    (Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Normal and Pathological Development of Melanocytes
    Université Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation radiobiologie et cancer
    Equipes Labellisées Ligue Contre le Cancer)

  • Jérémy H. Raymond

    (Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Normal and Pathological Development of Melanocytes
    Université Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation radiobiologie et cancer
    Equipes Labellisées Ligue Contre le Cancer)

  • Véronique Delmas

    (Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Normal and Pathological Development of Melanocytes
    Université Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation radiobiologie et cancer
    Equipes Labellisées Ligue Contre le Cancer)

  • Madeleine Le Coz

    (Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Normal and Pathological Development of Melanocytes
    Université Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation radiobiologie et cancer
    Equipes Labellisées Ligue Contre le Cancer)

  • Franck Gesbert

    (Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Normal and Pathological Development of Melanocytes
    Université Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation radiobiologie et cancer
    Equipes Labellisées Ligue Contre le Cancer)

  • Colin Kenny

    (University of Iowa)

  • Zackie Aktary

    (Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Normal and Pathological Development of Melanocytes
    Université Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation radiobiologie et cancer
    Equipes Labellisées Ligue Contre le Cancer)

  • Marie Pouteaux

    (Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Normal and Pathological Development of Melanocytes
    Université Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation radiobiologie et cancer
    Equipes Labellisées Ligue Contre le Cancer)

  • Florian Rambow

    (Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Normal and Pathological Development of Melanocytes
    Université Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation radiobiologie et cancer
    Equipes Labellisées Ligue Contre le Cancer)

  • Alain Sarasin

    (Université Paris-Sud)

  • Nisamanee Charoenchon

    (Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Normal and Pathological Development of Melanocytes
    Université Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation radiobiologie et cancer
    Equipes Labellisées Ligue Contre le Cancer
    Mahidol University)

  • Alfonso Bellacosa

    (Fox Chase Cancer Center)

  • Luis Sanchez-del-Campo

    (University of Oxford, Headington)

  • Laura Mosteo

    (University of Oxford, Headington)

  • Martin Lauss

    (Lund University and Skåne University Hospital)

  • Dies Meijer

    (University of Edinburgh)

  • Eirikur Steingrimsson

    (University of Iceland)

  • Göran B. Jönsson

    (Lund University and Skåne University Hospital)

  • Robert A. Cornell

    (University of Iowa)

  • Irwin Davidson

    (University of Iowa
    Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/UNISTRA)

  • Colin R. Goding

    (University of Oxford, Headington)

  • Lionel Larue

    (Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Normal and Pathological Development of Melanocytes
    Université Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation radiobiologie et cancer
    Equipes Labellisées Ligue Contre le Cancer)

Abstract

While the major drivers of melanoma initiation, including activation of NRAS/BRAF and loss of PTEN or CDKN2A, have been identified, the role of key transcription factors that impose altered transcriptional states in response to deregulated signaling is not well understood. The POU domain transcription factor BRN2 is a key regulator of melanoma invasion, yet its role in melanoma initiation remains unknown. Here, in a BrafV600E PtenF/+ context, we show that BRN2 haplo-insufficiency promotes melanoma initiation and metastasis. However, metastatic colonization is less efficient in the absence of Brn2. Mechanistically, BRN2 directly induces PTEN expression and in consequence represses PI3K signaling. Moreover, MITF, a BRN2 target, represses PTEN transcription. Collectively, our results suggest that on a PTEN heterozygous background somatic deletion of one BRN2 allele and temporal regulation of the other allele elicits melanoma initiation and progression.

Suggested Citation

  • Michael Hamm & Pierre Sohier & Valérie Petit & Jérémy H. Raymond & Véronique Delmas & Madeleine Le Coz & Franck Gesbert & Colin Kenny & Zackie Aktary & Marie Pouteaux & Florian Rambow & Alain Sarasin , 2021. "BRN2 is a non-canonical melanoma tumor-suppressor," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23973-5
    DOI: 10.1038/s41467-021-23973-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-23973-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-23973-5?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_s41467-021-23973-5. 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.