Spi-B-Mediated Silencing of Claudin-2 Promotes Early Dissemination of Lung Cancer Cells from Primary Tumors
Spi-B-Mediated Silencing of Claudin-2 Promotes Early Dissemination of Lung Cancer Cells from Primary Tumors
复制标题
Spi-B 介导的 Claudin-2 沉默促进肺癌细胞从原发肿瘤的早期扩散
DOI：
10.1158/0008-5472.can-17-0020
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发表时间：
2017-09-15
期刊：
影响因子：
11.2
通讯作者：
Liu, Zhe
中科院分区：
文献类型：
--
作者：
Du, Wei;Xu, Xing;Liu, Zhe
从上皮片层分离和通过周围间质的侵袭是上皮癌转移期间的关键早期事件。在这里，我们发现，淋巴细胞谱系限制性转录因子，Spi-B，经常在人肺癌组织中表达。表达Spi-B的癌细胞共表达波形蛋白，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、淋巴转移和总生存期短相关。从机制上讲，Spi-B破坏了细胞间连接，并通过重新配置紧密连接基因claudin-2（CLDN 2）的染色质结构并抑制其转录来增强侵袭性。这些数据表明，Spi-B参与间充质入侵，连接上皮癌转移与淋巴转录程序。(C)2017年AACR。
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 (CLDN2) and repressing its transcription. These data suggest that Spi-B participates in mesenchymal invasion, linking epithelial cancer metastasis with a lymphatic transcriptional program. (C) 2017 AACR.