FOXR2 Interacts with MYC to Promote Its Transcriptional Activities and Tumorigenesis.
FOXR2 Interacts with MYC to Promote Its Transcriptional Activities and Tumorigenesis.
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DOI：
10.1016/j.celrep.2016.06.004
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发表时间：
2016-07-12
期刊：
影响因子：
8.8
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Li X;Wang W;Xi Y;Gao M;Tran M;Aziz KE;Qin J;Li W;Chen J
将人类转录因子相互作用网络的大规模蛋白质组学分析结果与知识数据库相结合，我们确定FOXR2是排名第一的候选原癌基因之一。在这里，我们发现FOXR2与MYC和MAX形成稳定的复合物，并随后通过促进MYC的转录活性来调节细胞增殖。我们证明FOXR2在几种乳腺癌、肺癌和肝癌细胞系及相关患者肿瘤样本中高表达，而在异种移植模型中FOXR2表达的降低可抑制肿瘤生长。这些结果表明FOXR2与MYC一起促进癌细胞增殖，这是针对MYC驱动的癌症进行治疗干预的潜在肿瘤特异性靶点。
Combining the results of a large scale proteomic analysis of 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 demonstrated 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.