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.

ESDR477 - POU3F2 is a non-canonical tumor suppressor for melanoma

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.