BRN2 is a non-canonical melanoma tumor-suppressor
| العنوان: | BRN2 is a non-canonical melanoma tumor-suppressor |
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| المؤلفون: | Pierre Sohier, Luis Sánchez-del-Campo, Nisamanee Charoenchon, Colin Kenny, Madeleine Le Coz, Colin R. Goding, Lionel Larue, Véronique Delmas, Valérie Petit, Alain Sarasin, Eiríkur Steingrímsson, Zackie Aktary, Jérémy H. Raymond, Dies Meijer, Franck Gesbert, Michael Hamm, Irwin Davidson, Robert A. Cornell, Laura Mosteo, Florian Rambow, Alfonso Bellacosa, Göran Jönsson, Marie Pouteaux, Martin Lauss |
| المساهمون: | Signalisation normale et pathologique de l'embryon aux thérapies innovantes des cancers, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Carver College of Medicine [Iowa City], University of Iowa [Iowa City], Stabilité Génétique et Oncogenèse (UMR 8200), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Mahidol University [Bangkok], Fox Chase Cancer Center, University of Oxford [Oxford], Lund University [Lund], University of Edinburgh, University of Iceland [Reykjavik], Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Signalisation, radiobiologie et cancer, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Carver College of Medicine, University of Iowa, University of Oxford, delmas, veronique |
| المصدر: | Nature Communications, Vol 12, Iss 1, Pp 1-16 (2021) Nature Communications Nature Communications, Nature Publishing Group, 2021, 12 (1), pp.3707. ⟨10.1038/s41467-021-23973-5⟩ Nature Communications, Nature Publishing Group, 2021, 12, pp.3707. ⟨10.1038/s41467-021-23973-5⟩ 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, Jönsson, G B, Cornell, R A, Davidson, I, Goding, C R & Larue, L 2021, ' BRN2 is a non-canonical melanoma tumor-suppressor ', Nature Communications, vol. 12, no. 1, 3707 . https://doi.org/10.1038/s41467-021-23973-5Test Nature Communications, 2021, 12 (1), pp.3707. ⟨10.1038/s41467-021-23973-5⟩ |
| بيانات النشر: | Nature Portfolio, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Neuroblastoma RAS viral oncogene homolog, Skin Neoplasms, Carcinogenesis, [SDV]Life Sciences [q-bio], General Physics and Astronomy, Haploinsufficiency, Cohort Studies, Mice, Phosphatidylinositol 3-Kinases, 0302 clinical medicine, CDKN2A, Genes, Tumor Suppressor, RNA, Small Interfering, Melanoma, Multidisciplinary, biology, Microphthalmia-associated transcription factor, Immunohistochemistry, Gene Expression Regulation, Neoplastic, Mechanisms of disease, Gene Knockdown Techniques, 030220 oncology & carcinogenesis, Disease Progression, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Proto-Oncogene Proteins B-raf, Chromatin Immunoprecipitation, DNA Copy Number Variations, Science, Mice, Transgenic, [SDV.CAN]Life Sciences [q-bio]/Cancer, Context (language use), Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Animals, Humans, PTEN, Transcription factor, neoplasms, Cell Proliferation, Homeodomain Proteins, Microphthalmia-Associated Transcription Factor, POU domain, PTEN Phosphohydrolase, General Chemistry, Microarray Analysis, medicine.disease, Mice, Inbred C57BL, 030104 developmental biology, Mutation, POU Domain Factors, biology.protein, Cancer research, Gene expression |
| الوصف: | 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 BrafV600E PtenF/+ 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. The transcription factor BRN2 regulates melanoma migration and invasion, but its role during melanoma initiation is unclear. Here the authors show that BRN2 is a haplo-insufficient tumour suppressor that positively regulates PTEN expression and in the context of BRAF mutation and heterozygous PTEN, BRN2 loss promotes melanoma initiation and progression. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a798cbe1ae90c381ca35cfce2e74c937Test https://doaj.org/article/963d00b98bc54a4ea97659da7f5bc553Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a798cbe1ae90c381ca35cfce2e74c937 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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