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  • Hamm, MichaelUniversity of Paris-Saclay,PSL University (author)

BRN2 is a non-canonical melanoma tumor-suppressor

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • 2021-06-17
  • Springer Science and Business Media LLC,2021

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:9a0b647d-aff4-4e08-9223-bc539345f605
  • https://lup.lub.lu.se/record/9a0b647d-aff4-4e08-9223-bc539345f605URI
  • https://doi.org/10.1038/s41467-021-23973-5DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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 BrafV600EPtenF/+ 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Sohier, PierreUniversity of Paris-Saclay,PSL University (author)
  • Petit, ValériePSL University,University of Paris-Saclay (author)
  • Raymond, Jérémy H.University of Paris-Saclay,PSL University (author)
  • Delmas, VéroniquePSL University,University of Paris-Saclay (author)
  • Le Coz, MadeleineUniversity of Paris-Saclay,PSL University (author)
  • Gesbert, FranckUniversity of Paris-Saclay,PSL University (author)
  • Kenny, ColinUniversity of Iowa (author)
  • Aktary, ZackieUniversity of Paris-Saclay,PSL University (author)
  • Pouteaux, MariePSL University,University of Paris-Saclay (author)
  • Rambow, FlorianUniversity of Paris-Saclay,PSL University (author)
  • Sarasin, AlainStabilite genetique et oncogenese (author)
  • Charoenchon, NisamaneePSL University,University of Paris-Saclay,Mahidol University (author)
  • Bellacosa, AlfonsoFox Chase Cancer Center (author)
  • Sanchez-del-Campo, LuisUniversity of Oxford (author)
  • Mosteo, LauraUniversity of Oxford (author)
  • Lauss, MartinLund University,Lunds universitet,Melanoma Genomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Melanom,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Melanoma,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital(Swepub:lu)med-mlu (author)
  • Meijer, DiesUniversity of Edinburgh (author)
  • Steingrimsson, EirikurUniversity of Iceland (author)
  • Jönsson, Göran B.Lund University,Lunds universitet,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Melanoma Genomics,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Melanom,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lund Melanoma Study Group,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Melanoma,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital(Swepub:lu)onk-gjo (author)
  • Cornell, Robert A.University of Iowa (author)
  • Davidson, IrwinCentre d'Ecologie Fonctionnelle et Evolutive (CEFE) (author)
  • Goding, Colin R.University of Oxford (author)
  • Larue, LionelUniversity of Paris-Saclay,PSL University (author)
  • University of Paris-SaclayPSL University (creator_code:org_t)

Related titles

  • In:Nature Communications: Springer Science and Business Media LLC12:12041-1723

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