Identification of a link between Wnt/β-catenin signalling and the cell fusion pathway
Identification of a link between Wnt/β-catenin signalling and the cell fusion pathway
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DOI：
10.1038/ncomms1551
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发表时间：
2011-11-01
影响因子：
16.6
通讯作者：
Akiyama, Tetsu
中科院分区：
文献类型：
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作者：
Matsuura, Ken;Jigami, Takafumi;Akiyama, Tetsu
细胞融合在各种发育过程、免疫反应、组织稳态和再生，甚至可能在癌症中发挥关键作用。然而，调控细胞融合的信号仍然知之甚少。在筛选Wnt/ β -连环蛋白信号传导的新靶点时，我们发现了缺失1 （GCM1）的胶质细胞，GCM1编码一种参与表观遗传调控的转录因子，对合胞滋养层细胞（ST）的融合至关重要。本研究表明，β -连环蛋白/ bcl9样蛋白(BCL9L)/ t细胞因子4 （TCF4）信号直接靶向GCM1/合胞素通路，从而调节人绒毛膜癌细胞的融合。此外，我们发现GCM1/syncytin-B通路在bcl9l缺陷小鼠胎盘中显著下调，ST-II细胞的融合和分化被阻断。我们的研究结果证明了调节细胞融合的信号转导途径，并可能为涉及细胞融合的各种生物和病理过程提供有趣的视角。
Cell fusion has a critical role in various developmental processes, immune response, tissue homeostasis and regeneration, and possibly, in cancer. However, the signals that regulate cell fusion remain poorly understood. In a screen for novel targets of Wnt/beta-catenin signalling, we identified glial cells missing 1 (GCM1), which encodes a transcription factor that is involved in epigenetic regulation and is critical for the fusion of syncytiotrophoblast (ST) cells. Here we show that beta-catenin/BCL9-Like (BCL9L)/T-cell factor 4 (TCF4) signalling directly targets the GCM1/syncytin pathway and thereby regulates the fusion of human choriocarcinoma cells. Furthermore, we show that the GCM1/syncytin-B pathway is significantly downregulated in the placenta of BCL9L-deficient mice and that the fusion and differentiation of ST-II cells are blocked. Our results demonstrate a signal transduction pathway that regulates cell fusion, and may provide intriguing perspectives into the various biological and pathological processes that involve cell fusion.