title: Endothelial cell-derived fibronectin extra domain A promotes colorectal cancer metastasis via inducing epithelial-mesenchymal transition.
abstract: 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 α9β1 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.
authors.affiliation: Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China, Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA and Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Ou
authors.affiliation: Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China, Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA and Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China, Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA and Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Deng
authors.affiliation: Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China, Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA and Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Hongming
authors.initials: H
authors.lastname: Miao
authors.affiliation: Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China, Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA and Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China, Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA and Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Zha
authors.affiliation: Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China, Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA and Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Rongbin
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA and.
authors.forename: Liqing
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Hang
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China, Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA and Department of Biology, Georgia State University, Atlanta, GA 30303, USA lianghoujie@sina.com.
authors.forename: Houjie
authors.initials: H
authors.lastname: Liang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D005353:Fibronectins; D016023:Integrins; C107953:RAC1 protein, human; D012333:RNA, Messenger; C574442:extra domain A fibronectin, human; C113256:integrin alpha 9 beta 1; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D020830:rac1 GTP-Binding Protein