AP-2alpha-mediated activation of E2F and EZH2 drives melanoma metastasis

Cancer ResearchWhite JR, Thompson DT, Koch KE, et al. | July 02, 2021

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To clarify the role of the AP-2alpha transcription factor, which is encoded by TFAP2A, in melanoma metastasis, researchers undertook this study. They found that via transcriptional activation of genes within the E2F pathway, including EZH2, AP-2alpha facilitated melanoma metastasis. An interaction of AP-2alpha with members of the nucleosome remodeling and deacetylase complex was identified in a BioID screen. Not only a substantial decrease in anchorage-independent colony formation was caused by tazemetostat treatment (an FDA-approved and highly specific EZH2 inhibitor) in melanoma cells but also it showed heritable anti-metastatic impacts, which relied on AP-2alpha. Overall, findings revealed that AP-2alpha/EZH2 pathway drives melanoma metastasis, and AP-2alpha expression was shown to have utility as a biomarker to predict responsiveness to EZH2 inhibitors for the management of advanced melanomas.

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