Department of Immunology, Biochemistry and Molecular Biology, Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
School of Medical Laboratory, Tianjin Medical University, Tianjin, China.
Cancer Res. 2017 Sep 15;77(18):4809-4822. doi: 10.1158/0008-5472.CAN-17-0020. Epub 2017 Jul 28.
Dissociation from epithelial sheets and invasion through the surrounding stroma are critical early events during epithelial cancer metastasis. Here we find that a lymphocyte lineage-restricted transcription factor, Spi-B, is frequently expressed in human lung cancer tissues. The Spi-B-expressing cancer cells coexpressed vimentin but repressed E-cadherin and exhibited invasive behavior. Increased Spi-B expression was associated with tumor grade, lymphatic metastasis, and short overall survival. Mechanistically, Spi-B disrupted intercellular junctions and enhanced invasiveness by reconfiguring the chromatin structure of the tight junction gene claudin-2 () and repressing its transcription. These data suggest that Spi-B participates in mesenchymal invasion, linking epithelial cancer metastasis with a lymphatic transcriptional program. .
上皮细胞从上皮组织解离并浸润周围基质是上皮癌转移过程中的关键早期事件。在这里，我们发现淋巴细胞谱系特异性转录因子 Spi-B 在人肺癌组织中经常表达。表达 Spi-B 的癌细胞共同表达波形蛋白，但抑制 E-钙粘蛋白并表现出侵袭行为。Spi-B 表达增加与肿瘤分级、淋巴转移和总生存时间短有关。在机制上，Spi-B 通过重新配置紧密连接基因 claudin-2 的染色质结构并抑制其转录来破坏细胞间连接并增强侵袭性。这些数据表明 Spi-B 参与间充质浸润，将上皮癌转移与淋巴转录程序联系起来。
