FOXR2 Interacts with MYC to Promote Its Transcriptional Activities and Tumorigenesis

• FOXR2 associates with the MYC-MAX complex
• FOXR2 promotes cell proliferation by regulating MYC transcriptional activities
• FOXR2 is overexpressed in multiple cancers and patient tumor samples

SummaryBy combining the results of a large-scale proteomic analysis of the human transcription factor interaction network with knowledge databases, we identified FOXR2 as one of the top-ranked candidate proto-oncogenes. Here, we show that FOXR2 forms a stable complex with MYC and MAX and subsequently regulates cell proliferation by promoting MYC’s transcriptional activities. We demonstrate that FOXR2 is highly expressed in several breast, lung, and liver cancer cell lines and related patient tumor samples, while reduction of FOXR2 expression in a xenograft model inhibits tumor growth. These results indicate that FOXR2 acts with MYC to promote cancer cell proliferation, which is a potential tumor-specific target for therapeutic intervention against MYC-driven cancers.

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