BRN2 is a non-canonical melanoma tumor-suppressor

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

doi:10.1038/s41467-021-23973-5

BRN2 is a non-canonical melanoma tumor-suppressor

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. JönssonRobert A. Cornell, Irwin Davidson, Colin R. Goding, Lionel Larue

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

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^V600EPten^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.

Original language	English
Article number	3707
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-23973-5
Publication status	Published - 1 Dec 2021
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41467-021-23973-5

Cite this

Hamm, M., Sohier, P., Petit, V., Raymond, J. H., Delmas, V., Le Coz, M., Gesbert, F., Kenny, C., Aktary, Z., Pouteaux, M., Rambow, F., Sarasin, A., Charoenchon, N., Bellacosa, A., Sanchez-del-Campo, L., Mosteo, L., Lauss, M., Meijer, D., Steingrimsson, E., ... Larue, L. (2021). BRN2 is a non-canonical melanoma tumor-suppressor. Nature Communications, 12(1), Article 3707. https://doi.org/10.1038/s41467-021-23973-5

@article{258b1184b8514442b470b149b2410566,

title = "BRN2 is a non-canonical melanoma tumor-suppressor",

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.",

author = "Michael Hamm and Pierre Sohier and Val{\'e}rie Petit and Raymond, {J{\'e}r{\'e}my H.} and V{\'e}ronique Delmas and {Le Coz}, Madeleine and Franck Gesbert and Colin Kenny and Zackie Aktary and Marie Pouteaux and Florian Rambow and Alain Sarasin and Nisamanee Charoenchon and Alfonso Bellacosa and Luis Sanchez-del-Campo and Laura Mosteo and Martin Lauss and Dies Meijer and Eirikur Steingrimsson and J{\"o}nsson, {G{\"o}ran B.} and Cornell, {Robert A.} and Irwin Davidson and Goding, {Colin R.} and Lionel Larue",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = dec,

day = "1",

doi = "10.1038/s41467-021-23973-5",

language = "English",

volume = "12",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

Hamm, M, Sohier, P, Petit, V, Raymond, JH, Delmas, V, Le Coz, M, Gesbert, F, Kenny, C, Aktary, Z, Pouteaux, M, Rambow, F, Sarasin, A, Charoenchon, N, Bellacosa, A, Sanchez-del-Campo, L, Mosteo, L, Lauss, M, Meijer, D, Steingrimsson, E, Jönsson, GB, Cornell, RA, Davidson, I, Goding, CR & Larue, L 2021, 'BRN2 is a non-canonical melanoma tumor-suppressor', Nature Communications, vol. 12, no. 1, 3707. https://doi.org/10.1038/s41467-021-23973-5

TY - JOUR

T1 - BRN2 is a non-canonical melanoma tumor-suppressor

AU - Hamm, Michael

AU - Sohier, Pierre

AU - Petit, Valérie

AU - Raymond, Jérémy H.

AU - Delmas, Véronique

AU - Le Coz, Madeleine

AU - Gesbert, Franck

AU - Kenny, Colin

AU - Aktary, Zackie

AU - Pouteaux, Marie

AU - Rambow, Florian

AU - Sarasin, Alain

AU - Charoenchon, Nisamanee

AU - Bellacosa, Alfonso

AU - Sanchez-del-Campo, Luis

AU - Mosteo, Laura

AU - Lauss, Martin

AU - Meijer, Dies

AU - Steingrimsson, Eirikur

AU - Jönsson, Göran B.

AU - Cornell, Robert A.

AU - Davidson, Irwin

AU - Goding, Colin R.

AU - Larue, Lionel

PY - 2021/12/1

Y1 - 2021/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85108003528&partnerID=8YFLogxK

U2 - 10.1038/s41467-021-23973-5

DO - 10.1038/s41467-021-23973-5

M3 - Article

C2 - 34140478

AN - SCOPUS:85108003528

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3707

ER -

BRN2 is a non-canonical melanoma tumor-suppressor

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this