title: The role of TGFBI (βig-H3) in gastrointestinal tract tumorigenesis.
abstract: BACKGROUND
  TGFβ-induced (TGFBI/βig-H3) is a protein inducible by TGFβ1 and secreted by many types of cells. It binds to collagen, forms part of the extracellular matrix (ECM), and interacts with integrins on cell surfaces. In this study, we investigated the role of TGFBI in tumorigenesis and the underlying mechanisms.
  
  
  METHODS
  Patient serum TGFBI levels were determined by ELISA. TGFBI transgenic and gene knockout mice and TGFBI-overexpressing liver cells were used for mechanistic studies.
  
  
  RESULTS
  We demonstrated that patients with cholangiocarcinomas, hepatic carcinomas or gastric carcinomas presented significantly elevated serum TGFBI levels, and the excess TGFBI was derived from the tumor masses. TGFBI overexpression in mice resulted in increased incidence of spontaneous tumors and N,N-diethylnitrosamine (DEN)-induced liver tumor nodules, compared to that in wild type (WT) mice, while TGFBI knockout mice were comparable to WT controls in these 2 aspects. TGFBI promoted the survival of Aml-12 liver cells with DNA damage after irradiation, and augmented their post-irradiation proliferation. It activated the FAK/AKT/AKT1S1/PRS6/EIF4EBP pathway, which is known to modulate cell survival and proliferation.
  
  
  CONCLUSIONS
  Our data suggest that TGFBI functions as a promoter of certain gastrointestinal tract cancers. It provides a survival advantage to cells with DNA damage. Over a long time span, this advantage could translate into increased tumor risks.
authors.affiliation: Laboratory of Immunology and Cardiovascular Research, Centre hospitalier de l'Université de Montréal (CRCHUM), 900 Stain-Denis Street, Montreal, Quebec, Canada. icehan76@hotmail.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Zhejiang University, 88 Jiefang Road, Hangzhou, China. comethalley@hotmail.com.
authors.forename: Haolei
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Zhejiang University, 88 Jiefang Road, Hangzhou, China. chy1983@163.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Anatomic Pathology, AmeriPath Central Florida, 8150 Chancellor Dr, Orlando, FL, USA. bhu@ameripath.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Hu
authors.affiliation: Laboratory of Immunology and Cardiovascular Research, Centre hospitalier de l'Université de Montréal (CRCHUM), 900 Stain-Denis Street, Montreal, Quebec, Canada. hongyu.luo@umontreal.ca.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Zhejiang University, 88 Jiefang Road, Hangzhou, China. wuyulian@medmail.com.cn.
authors.forename: Yulian
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Laboratory of Immunology and Cardiovascular Research, Centre hospitalier de l'Université de Montréal (CRCHUM), 900 Stain-Denis Street, Montreal, Quebec, Canada. jianping.wu@umontreal.ca.|Nephrology Service, Research Centre, Centre hospitalier de l'Université de Montréal (CRCHUM), 900 Stain-Denis Street, Montreal, Quebec, Canada. jianping.wu@umontreal.ca.
authors.forename: Jiangping
authors.initials: J
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis; D063646:Carcinogenesis / Q000378:metabolism*; D002273:Carcinogens; D049109:Cell Proliferation; D002470:Cell Survival; D004249:DNA Damage; D016326:Extracellular Matrix Proteins / Q000097:blood / Q000378:metabolism*; D005770:Gastrointestinal Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology*; D041981:Gastrointestinal Tract / Q000473:pathology*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000097:blood / Q000378:metabolism*; D000099222:betaIG-H3 Protein
chemical_list: D002273:Carcinogens; D016326:Extracellular Matrix Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein