Endothelial cell-derived fibronectin extra domain A promotes colorectal cancer metastasis via inducing epithelial-mesenchymal transition
Endothelial cell-derived fibronectin extra domain A promotes colorectal cancer metastasis via inducing epithelial-mesenchymal transition
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DOI：
10.1093/carcin/bgu090
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发表时间：
2014-07-01
期刊：
影响因子：
4.7
通讯作者：
Liang, Houjie
中科院分区：
文献类型：
--
作者：
Ou, Juanjuan;Peng, Yuan;Liang, Houjie
近年来的研究表明，内皮细胞（endothelial cells，ECs）在包括结直肠癌（colorectal carcinoma，CRCs）在内的多种肿瘤的发病机制中发挥着重要作用，但其作用机制尚不清楚。我们以前已经证明，CRC衍生的纤连蛋白额外结构域A（EDA）促进CRC的血管生成，肿瘤发生和转移。在目前的研究中，我们发现EC分泌的EDA通过诱导上皮-间充质转化来促进CRC细胞的转移能力。体内外实验表明，EC分泌的EDA通过与邻近CRC细胞上的整合素α 9 β 1相互作用，激活黏着斑激酶和Rac信号，从而增强细胞骨架的极性，促进CRC细胞的侵袭能力。此外，Erk信号通路被揭示为关键介导EC衍生的EDA对CRC细胞的作用。我们的研究结果揭示了一种新的致癌作用的EC促进CRC恶性肿瘤通过分泌EDA。
Recent evidence has been suggesting the important roles of endothelial cells (ECs) involved in the pathogenesis of several cancers, including colorectal carcinomas (CRCs), but the underlying mechanism remains elusive. We have demonstrated previously that CRC-derived fibronectin extra domain A (EDA) promotes vasculogenesis, tumorigenesis and metastasis of CRCs. At the current study, we showed that EC-secreted EDA promotes the metastatic capacity CRC cells via inducing an epithelial-mesenchymal transition. In vitro and in vivo experiments showed that EC-secreted EDA, via the interaction with integrin a9 beta 1 on neighboring CRC cells, leads to the activation of focal adhesion kinase as well as Rac signalings, thus strengthens the polarity of cytoskeleton and promotes the invasion capacity of CRC cells. Furthermore, Erk signaling pathway was revealed to critically mediate the effect of EC-derived EDA on CRC cells. Our findings reveal a novel oncogenic role of ECs in promoting CRC malignancy through secreting EDA.