The cell competition-based high-throughput screening identifies small compounds that promote the elimination of RasV12-transformed cells from epithelia.
The cell competition-based high-throughput screening identifies small compounds that promote the elimination of RasV12-transformed cells from epithelia.
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DOI：
10.1038/srep15336
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发表时间：
2015-10-20
影响因子：
4.6
通讯作者：
Fujita Y
中科院分区：
文献类型：
--
作者：
Yamauchi H;Matsumaru T;Morita T;Ishikawa S;Maenaka K;Takigawa I;Semba K;Kon S;Fujita Y
最近的研究表明，正常上皮细胞和转化上皮细胞之间可能会发生细胞竞争。正常上皮细胞识别邻近转化细胞的存在并主动将它们从上皮组织中消除。在这里，我们建立了一个全新的针对细胞竞争的高通量筛选平台。通过使用这个平台，我们已经确定 Rebeccamycin 是一种有效化合物，可以特异性促进 RasV12 转化细胞从上皮细胞中的消除，尽管经过较长时间的治疗后，它对正常上皮细胞表现出显着的细胞毒性作用。在几种瑞贝卡霉素衍生物化合物中，我们发现VC1-8对正常细胞的细胞毒性最小，但对转化细胞的消除效果相当。 VC1-8 的这种细胞竞争促进活性在体外和离体均可观察到。这些数据表明，基于细胞竞争的筛选是建立新型癌症预防药物的有前途的工具。
Recent studies have revealed that cell competition can occur between normal and transformed epithelial cells; normal epithelial cells recognize the presence of the neighboring transformed cells and actively eliminate them from epithelial tissues. Here, we have established a brand-new high-throughput screening platform that targets cell competition. By using this platform, we have identified Rebeccamycin as a hit compound that specifically promotes elimination of RasV12-transformed cells from the epithelium, though after longer treatment it shows substantial cytotoxic effect against normal epithelial cells. Among several Rebeccamycin-derivative compounds, we have found that VC1-8 has least cytotoxicity against normal cells but shows the comparable effect on the elimination of transformed cells. This cell competition-promoting activity of VC1-8 is observed both in vitro and ex vivo. These data demonstrate that the cell competition-based screening is a promising tool for the establishment of a novel type of cancer preventive medicine.