Journal article
BRN2 is a non-canonical melanoma tumor-suppressor
Nature communications, Vol.12(1), pp.3707-3707
12/2021
DOI: 10.1038/s41467-021-23973-5
PMCID: PMC8211827
PMID: 34140478
Abstract
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 Braf V600E Pten F/+ 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.
Details
- Title: Subtitle
- BRN2 is a non-canonical melanoma tumor-suppressor
- Creators
- Michael Hamm - Institut CuriePierre Sohier - Institut CurieValérie Petit - Institut CurieJérémy Raymond - Institut CurieVéronique Delmas - Institut CurieMadeleine Le Coz - Institut CurieFranck Gesbert - Institut CurieColin Kenny - Roy J. and Lucille A. Carver College of MedicineZackie Aktary - Institut CurieMarie Pouteaux - Institut CurieFlorian Rambow - Institut CurieAlain Sarasin - Institut Gustave RoussyNisamanee Charoenchon - Institut CurieAlfonso Bellacosa - Fox Chase Cancer CenterLuis Sanchez-del-Campo - University of OxfordLaura Mosteo - University of OxfordMartin Lauss - Lund UniversityDies Meijer - University of EdinburghEirikur Steingrimsson - University of IcelandGöran Jönsson - Lund UniversityRobert Cornell - Roy J. and Lucille A. Carver College of MedicineIrwin Davidson - InsermColin Goding - University of OxfordLionel Larue - Institut Curie
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.12(1), pp.3707-3707
- DOI
- 10.1038/s41467-021-23973-5
- PMID
- 34140478
- PMCID
- PMC8211827
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Publisher
- Nature Publishing Group
- Grant note
- DOI: 10.13039/501100004097, name: Fondation ARC pour la Recherche sur le Cancer, award: 00
- Language
- English
- Date published
- 12/2021
- Academic Unit
- Anatomy and Cell Biology; Surgery
- Record Identifier
- 9984322795302771
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