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- W4309479221 abstract "While the main drivers of melanoma initiation, including NRAS/BRAF activation 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 POU3F2/BRN2 domain transcription factor is a key regulator of melanoma invasion, but its role in melanoma initiation remains unknown. Here, in a BrafV600E PtenF/+ context, we show that BRN2 haploinsufficiency promotes melanoma initiation and metastasis. However, metastatic colonization is less efficient in the absence of Brn2. Mechanistically, BRN2 directly induces PTEN expression and consequently represses PI3K signaling. In addition, MITF, a target of BRN2, represses PTEN transcription. Collectively, our results suggest that in a PTEN heterozygous background, somatic deletion of one BRN2 allele and temporal regulation of the other allele cause melanoma initiation and progression." @default.
- W4309479221 created "2022-11-28" @default.
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- W4309479221 date "2022-12-01" @default.
- W4309479221 modified "2023-09-25" @default.
- W4309479221 title "477 POU3F2 is a non-canonical tumor suppressor for melanoma" @default.
- W4309479221 doi "https://doi.org/10.1016/j.jid.2022.09.491" @default.
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