Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

BRN2 is a non-canonical melanoma tumor-suppressor

Hamm, Michael ; Sohier, Pierre ; Petit, Valérie ; Raymond, Jérémy H. ; Delmas, Véronique ; Le Coz, Madeleine ; Gesbert, Franck ; Kenny, Colin ; Aktary, Zackie and Pouteaux, Marie , et al. (2021) In Nature Communications 12(1).
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 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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
@article{9a0b647d-aff4-4e08-9223-bc539345f605,
  abstract     = {{<p>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 Braf<sup>V600E</sup>Pten<sup>F/+</sup> 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.</p>}},
  author       = {{Hamm, Michael and Sohier, Pierre and Petit, Valérie and Raymond, Jérémy H. and Delmas, Véronique and Le Coz, Madeleine and Gesbert, Franck and Kenny, Colin and Aktary, Zackie and Pouteaux, Marie and Rambow, Florian and Sarasin, Alain and Charoenchon, Nisamanee and Bellacosa, Alfonso and Sanchez-del-Campo, Luis and Mosteo, Laura and Lauss, Martin and Meijer, Dies and Steingrimsson, Eirikur and Jönsson, Göran B. and Cornell, Robert A. and Davidson, Irwin and Goding, Colin R. and Larue, Lionel}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{BRN2 is a non-canonical melanoma tumor-suppressor}},
  url          = {{http://dx.doi.org/10.1038/s41467-021-23973-5}},
  doi          = {{10.1038/s41467-021-23973-5}},
  volume       = {{12}},
  year         = {{2021}},
}