BRN2 is a non-canonical melanoma tumor-suppressor.

BRN2 is a non-canonical melanoma tumor-suppressor.

Publication date: Jun 17, 2021

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 Pten 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.

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Concepts Keywords
Cdkn2a CDKN2A
Drivers PTEN
Efficient Melanoma
Heterozygous Cancer
Tumor Transcription factors
Enzymes
Branches of biology
Microphthalmia-associated transcription factor
C-Met
MTOR
BRAF

Semantics

Type Source Name
disease MESH melanoma
pathway KEGG Melanoma
disease MESH tumor
drug DRUGBANK Coenzyme M
disease MESH senescence
disease MESH skin cancer
disease MESH glioblastoma
disease MESH neuroblastoma
disease MESH Microphthalmia
disease MESH repression
disease MESH noma
disease MESH nevi
drug DRUGBANK Topiramate
drug DRUGBANK Honey
drug DRUGBANK L-Tyrosine
drug DRUGBANK Tamoxifen
disease MESH growth
drug DRUGBANK Broxuridine
disease MESH tumorigenesis
drug DRUGBANK Trestolone
disease MESH lentivirus infection
pathway REACTOME Immune System
disease MESH hyperpigmentation
drug DRUGBANK Proline
drug DRUGBANK Albendazole
pathway KEGG Apoptosis
drug DRUGBANK L-Phenylalanine
disease MESH heterozygotes
disease MESH lung cancer
drug DRUGBANK Pentaerythritol tetranitrate
drug DRUGBANK Water
disease MESH Community
drug DRUGBANK Tromethamine
drug DRUGBANK Dimethyl sulfoxide
drug DRUGBANK Phosphate ion
drug DRUGBANK Nitrogen
drug DRUGBANK Sodium Citrate
drug DRUGBANK Human Serum Albumin
drug DRUGBANK Biotin
drug DRUGBANK Ranitidine
drug DRUGBANK Streptomycin
drug DRUGBANK Alteplase
drug DRUGBANK Binimetinib
drug DRUGBANK Gentian violet cation
drug DRUGBANK Ethanol
drug DRUGBANK Sodium lauryl sulfate
drug DRUGBANK Edetic Acid
drug DRUGBANK Phenol
drug DRUGBANK Trimebutine
drug DRUGBANK Methylergometrine
drug DRUGBANK Rasagiline
pathway KEGG Cellular senescence
disease MESH melanocytic nevi
drug DRUGBANK Bismuth subgallate
disease MESH Waardenburg syndrome
disease MESH intestinal pseudoobstruction
disease MESH chromosome abnormalities
disease MESH genomic stability
drug DRUGBANK Etoperidone
disease MESH ARC
drug DRUGBANK 3 7 11 15-Tetramethyl-Hexadecan-1-Ol
drug DRUGBANK Folic Acid

Original Article

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