Publication: BRN2 is a non-canonical melanoma tumor-suppressor
Issued Date
2021-12-01
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ISSN
20411723
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2-s2.0-85108003528
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Mahidol University
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SCOPUS
Bibliographic Citation
Nature Communications. Vol.12, No.1 (2021)
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, Nisamanee Charoenchon, Alfonso Bellacosa, Luis Sanchez-del-Campo, Laura Mosteo, Martin Lauss, Dies Meijer, Eirikur Steingrimsson, Göran B. Jönsson, Robert A. Cornell, Irwin Davidson, Colin R. Goding, Lionel Larue BRN2 is a non-canonical melanoma tumor-suppressor. Nature Communications. Vol.12, No.1 (2021). doi:10.1038/s41467-021-23973-5 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/75932
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Title
BRN2 is a non-canonical melanoma tumor-suppressor
Author(s)
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
Nisamanee Charoenchon
Alfonso Bellacosa
Luis Sanchez-del-Campo
Laura Mosteo
Martin Lauss
Dies Meijer
Eirikur Steingrimsson
Göran B. Jönsson
Robert A. Cornell
Irwin Davidson
Colin R. Goding
Lionel Larue
Pierre Sohier
Valérie Petit
Jérémy H. Raymond
Véronique Delmas
Madeleine Le Coz
Franck Gesbert
Colin Kenny
Zackie Aktary
Marie Pouteaux
Florian Rambow
Alain Sarasin
Nisamanee Charoenchon
Alfonso Bellacosa
Luis Sanchez-del-Campo
Laura Mosteo
Martin Lauss
Dies Meijer
Eirikur Steingrimsson
Göran B. Jönsson
Robert A. Cornell
Irwin Davidson
Colin R. Goding
Lionel Larue
Other Contributor(s)
Université PSL
Universite Paris-Saclay
Læknadeild Háskóla Íslands
Institut de Cancerologie Gustave Roussy
The University of Edinburgh
Skånes universitetssjukhus
Mahidol University
University of Iowa Carver College of Medicine
Fox Chase Cancer Center
Nuffield Department of Medicine
CNRS Centre National de la Recherche Scientifique
Equipe Labellisée Ligue Contre le Cancer
Universite Paris-Saclay
Læknadeild Háskóla Íslands
Institut de Cancerologie Gustave Roussy
The University of Edinburgh
Skånes universitetssjukhus
Mahidol University
University of Iowa Carver College of Medicine
Fox Chase Cancer Center
Nuffield Department of Medicine
CNRS Centre National de la Recherche Scientifique
Equipe Labellisée 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 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.