Matches in SemOpenAlex for { <https://semopenalex.org/work/W3119193957> ?p ?o ?g. }
- W3119193957 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, we show that BRN2 haplo-insufficiency is sufficient to promote melanoma initiation and metastasis, acting as a non-canonical tumor suppressor. Mechanistically, BRN2 directly modulates PTEN expression, and PI3K signaling, to drive tumor initiation and progression. Collectively our results reveal that somatic deletion of one BRN2 allele elicits melanoma initiation and progression. SIGNIFICANCE Here, we report frequent mono-allelic loss of the transcription factor BRN2 in human cutaneous melanoma metastases. We developed a mouse model for Brn2-deficient melanoma based on the most common alterations ( Braf V600E and Pten loss) in human melanoma and established the role of Brn2 as a functional regulator of tumor initiation, tumor growth, and the formation of metastases in vivo . Mechanistically, BRN2 loss increases PI3K-signaling through PTEN repression, either via MITF induction or not. Overall, we describe a novel tumor suppressor of high prevalence in human melanoma that regulates several steps of in vivo melanomagenesis through two previously unknown molecular mechanisms." @default.
- W3119193957 created "2021-01-18" @default.
- W3119193957 creator A5002451432 @default.
- W3119193957 creator A5006037534 @default.
- W3119193957 creator A5007668011 @default.
- W3119193957 creator A5010280122 @default.
- W3119193957 creator A5010579277 @default.
- W3119193957 creator A5013152084 @default.
- W3119193957 creator A5022715455 @default.
- W3119193957 creator A5023274542 @default.
- W3119193957 creator A5023829156 @default.
- W3119193957 creator A5024573531 @default.
- W3119193957 creator A5028824170 @default.
- W3119193957 creator A5034389010 @default.
- W3119193957 creator A5035729379 @default.
- W3119193957 creator A5037227386 @default.
- W3119193957 creator A5037577234 @default.
- W3119193957 creator A5038549031 @default.
- W3119193957 creator A5050913896 @default.
- W3119193957 creator A5055122504 @default.
- W3119193957 creator A5060636893 @default.
- W3119193957 creator A5073807427 @default.
- W3119193957 creator A5086467183 @default.
- W3119193957 creator A5087007057 @default.
- W3119193957 creator A5090976877 @default.
- W3119193957 date "2021-01-13" @default.
- W3119193957 modified "2023-10-18" @default.
- W3119193957 title "BRN2 is a non-canonical melanoma tumor-suppressor" @default.
- W3119193957 cites W1540676355 @default.
- W3119193957 cites W1546293603 @default.
- W3119193957 cites W1598759112 @default.
- W3119193957 cites W1854900052 @default.
- W3119193957 cites W1867333488 @default.
- W3119193957 cites W1893275964 @default.
- W3119193957 cites W1951808778 @default.
- W3119193957 cites W1967660850 @default.
- W3119193957 cites W1970195561 @default.
- W3119193957 cites W1973569563 @default.
- W3119193957 cites W1977679887 @default.
- W3119193957 cites W1977889613 @default.
- W3119193957 cites W1978113416 @default.
- W3119193957 cites W1978139115 @default.
- W3119193957 cites W1979188008 @default.
- W3119193957 cites W2017463214 @default.
- W3119193957 cites W2019544036 @default.
- W3119193957 cites W2029665825 @default.
- W3119193957 cites W2029848679 @default.
- W3119193957 cites W2035854437 @default.
- W3119193957 cites W2035939293 @default.
- W3119193957 cites W2046585589 @default.
- W3119193957 cites W2049657352 @default.
- W3119193957 cites W2050839565 @default.
- W3119193957 cites W2060723553 @default.
- W3119193957 cites W2062527245 @default.
- W3119193957 cites W2068289276 @default.
- W3119193957 cites W2070050178 @default.
- W3119193957 cites W2093240609 @default.
- W3119193957 cites W2096860625 @default.
- W3119193957 cites W2097010979 @default.
- W3119193957 cites W2097198003 @default.
- W3119193957 cites W2100725331 @default.
- W3119193957 cites W2104503053 @default.
- W3119193957 cites W2112572166 @default.
- W3119193957 cites W2121886536 @default.
- W3119193957 cites W2122845914 @default.
- W3119193957 cites W2131001269 @default.
- W3119193957 cites W2131790747 @default.
- W3119193957 cites W2133067361 @default.
- W3119193957 cites W2135547577 @default.
- W3119193957 cites W2140008764 @default.
- W3119193957 cites W2144161917 @default.
- W3119193957 cites W2163188200 @default.
- W3119193957 cites W2168820637 @default.
- W3119193957 cites W2169744057 @default.
- W3119193957 cites W2540786849 @default.
- W3119193957 cites W2594897444 @default.
- W3119193957 cites W2803957288 @default.
- W3119193957 cites W2818473048 @default.
- W3119193957 cites W2916900413 @default.
- W3119193957 doi "https://doi.org/10.1101/2021.01.13.426554" @default.
- W3119193957 hasPublicationYear "2021" @default.
- W3119193957 type Work @default.
- W3119193957 sameAs 3119193957 @default.
- W3119193957 citedByCount "0" @default.
- W3119193957 crossrefType "posted-content" @default.
- W3119193957 hasAuthorship W3119193957A5002451432 @default.
- W3119193957 hasAuthorship W3119193957A5006037534 @default.
- W3119193957 hasAuthorship W3119193957A5007668011 @default.
- W3119193957 hasAuthorship W3119193957A5010280122 @default.
- W3119193957 hasAuthorship W3119193957A5010579277 @default.
- W3119193957 hasAuthorship W3119193957A5013152084 @default.
- W3119193957 hasAuthorship W3119193957A5022715455 @default.
- W3119193957 hasAuthorship W3119193957A5023274542 @default.
- W3119193957 hasAuthorship W3119193957A5023829156 @default.
- W3119193957 hasAuthorship W3119193957A5024573531 @default.
- W3119193957 hasAuthorship W3119193957A5028824170 @default.
- W3119193957 hasAuthorship W3119193957A5034389010 @default.
- W3119193957 hasAuthorship W3119193957A5035729379 @default.
- W3119193957 hasAuthorship W3119193957A5037227386 @default.
- W3119193957 hasAuthorship W3119193957A5037577234 @default.