The retinoic acid inducible transcription factor AP-2α, encoded by TFAP2A, is required by migratory neural crest cells. There has been interest in defining the role of AP-2α in metastatic melanoma cells, which share many features of neural crest cells, however, the role of AP-2α remains controversial. Some findings suggest AP-2α functions as a tumor suppressor while others have reported high expression correlates with poor prognosis. White and colleagues demonstrated that AP-2α enhances melanoma metastasis through transcriptional activation of E2F pathway genes including EZH2, a methyltransferase with known oncogenic properties. Mechanistically, AP-2α promotes transcription of these target genes via inhibition of the NuRD repression complex, which regulates chromatin remodeling. Pharmacological inhibition of EZH2 with tazemetostat was effective at reducing anchorage-independent colony formation in vitro and metastasis in vivo, supporting the importance of this pathway in facilitating melanoma cell invasion.

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