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

Juanjuan Ou; Yuan Peng; Jia Deng; Hongming Miao; Jie Zhou; Lin Zha; Rongbin Zhou; Liqing Yu; Hang Shi; Houjie Liang

doi:10.1093/carcin/bgu090

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

Carcinogenesis. 2014 Jul;35(7):1661-70. doi: 10.1093/carcin/bgu090. Epub 2014 Apr 17.

Authors

Juanjuan Ou¹, Yuan Peng¹, Jia Deng¹, Hongming Miao¹, Jie Zhou¹, Lin Zha¹, Rongbin Zhou¹, Liqing Yu², Hang Shi³, Houjie Liang⁴

Affiliations

¹ 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.
² Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA and.
³ Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
⁴ 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.

PMID: 24743511
DOI: 10.1093/carcin/bgu090

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blotting, Western
Cell Movement
Cell Proliferation
Colorectal Neoplasms / genetics
Colorectal Neoplasms / metabolism
Colorectal Neoplasms / pathology*
Endothelium, Vascular / metabolism
Endothelium, Vascular / pathology*
Epithelial-Mesenchymal Transition*
Fibronectins / genetics
Fibronectins / metabolism*
Fluorescent Antibody Technique
Focal Adhesion Kinase 1 / genetics
Focal Adhesion Kinase 1 / metabolism
Humans
Immunoenzyme Techniques
Immunoprecipitation
Integrins / genetics
Integrins / metabolism
Liver Neoplasms / genetics
Liver Neoplasms / metabolism
Liver Neoplasms / secondary*
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Invasiveness
RNA, Messenger / genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
rac1 GTP-Binding Protein / genetics
rac1 GTP-Binding Protein / metabolism

Substances

Fibronectins
Integrins
RAC1 protein, human
RNA, Messenger
extra domain A fibronectin, human
integrin alpha 9 beta 1
Focal Adhesion Kinase 1
PTK2 protein, human
rac1 GTP-Binding Protein