Endothelial cell-derived fibronectin extra domain A promotes colorectal cancer metastasis via inducing epithelial-mesenchymal transition

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.