BRN2, a POUerful driver of melanoma phenotype switching and metastasis

Mitchell E. Fane, Yash Chhabra, Aaron G. Smith, Richard A. Sturm

Research output: Contribution to journalReview articlepeer-review

18 Scopus citations


The POU domain family of transcription factors play a central role in embryogenesis and are highly expressed in neural crest cells and the developing brain. BRN2 is a class III POU domain protein that is a key mediator of neuroendocrine and melanocytic development and differentiation. While BRN2 is a central regulator in numerous developmental programs, it has also emerged as a major player in the biology of tumourigenesis. In melanoma, BRN2 has been implicated as one of the master regulators of the acquisition of invasive behaviour within the phenotype switching model of progression. As a mediator of melanoma cell phenotype switching, it coordinates the transition to a dedifferentiated, slow cycling and highly motile cell type. Its inverse expression relationship with MITF is believed to mediate tumour progression and metastasis within this model. Recent evidence has now outlined a potential epigenetic switching mechanism in melanoma cells driven by BRN2 expression that induces melanoma cell invasion. We summarize the role of BRN2 in tumour cell dissemination and metastasis in melanoma, while also examining it as a potential metastatic regulator in other tumour models.

Original languageEnglish (US)
Pages (from-to)9-24
Number of pages16
JournalPigment Cell and Melanoma Research
Issue number1
StatePublished - Jan 2019
Externally publishedYes


  • CDKN2A
  • POU
  • epigenetic
  • phenotype switching
  • transcription factor

ASJC Scopus subject areas

  • Oncology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Dermatology


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