title: Hepatocyte autotaxin expression promotes liver fibrosis and cancer.
abstract: Autotaxin (ATX) is a secreted lysophospholipase D that catalyzes the production of lysophosphatidic acid (LPA), a pleiotropic growth-factor-like lysophospholipid. Increased ATX expression has been detected in various chronic inflammatory disorders and different types of cancer; however, little is known about its role and mode of action in liver fibrosis and cancer. Here, increased ATX expression was detected in chronic liver disease (CLD) patients of different etiologies, associated with shorter overall survival. In mice, different hepatotoxic stimuli linked with the development of different forms of CLDs were shown to stimulate hepatocyte ATX expression, leading to increased LPA levels, activation of hepatic stellate cells (HSCs), and amplification of profibrotic signals. Hepatocyte-specific, conditional genetic deletion and/or transgenic overexpression of ATX established a liver profibrotic role for ATX/LPA, whereas pharmacological ATX inhibition studies suggested ATX as a possible therapeutic target in CLDs. In addition, hepatocyte ATX ablation and the consequent deregulation of lipid homeostasis was also shown to attenuate hepatocellular carcinoma (HCC) development, thus implicating ATX/LPA in the causative link of cirrhosis and HCC.
  
  
  
  ATX is a novel player in the pathogenesis of liver fibrosis and cancer and a promising therapeutic target. (Hepatology 2017;65:1369-1383).
authors.affiliation: Division of Immunology, Biomedical Sciences Research Center Alexander Fleming, Athens, Greece.
authors.forename: Eleanna
authors.initials: E
authors.lastname: Kaffe
authors.affiliation: Division of Immunology, Biomedical Sciences Research Center Alexander Fleming, Athens, Greece.
authors.forename: Aggeliki
authors.initials: A
authors.lastname: Katsifa
authors.affiliation: Division of Immunology, Biomedical Sciences Research Center Alexander Fleming, Athens, Greece.
authors.forename: Nikos
authors.initials: N
authors.lastname: Xylourgidis
authors.affiliation: Division of Immunology, Biomedical Sciences Research Center Alexander Fleming, Athens, Greece.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Ninou
authors.affiliation: Division of Immunology, Biomedical Sciences Research Center Alexander Fleming, Athens, Greece.
authors.forename: Markella
authors.initials: M
authors.lastname: Zannikou
authors.affiliation: Division of Immunology, Biomedical Sciences Research Center Alexander Fleming, Athens, Greece.
authors.forename: Vaggelis
authors.initials: V
authors.lastname: Harokopos
authors.affiliation: Laboratory of Molecular Virology, Hellenic Pasteur Institute, Athens, Greece.
authors.forename: Pelagia
authors.initials: P
authors.lastname: Foka
authors.affiliation: Laboratory of Molecular Virology, Hellenic Pasteur Institute, Athens, Greece.
authors.forename: Alexios
authors.initials: A
authors.lastname: Dimitriadis
authors.affiliation: Department of Histology and Embryology, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Kostas
authors.initials: K
authors.lastname: Evangelou
authors.affiliation: Laboratory of Biochemistry, Technological Educational Institute of Thessaly, Larissa, Greece.
authors.forename: Anargyros N
authors.initials: AN
authors.lastname: Moulas
authors.affiliation: Laboratory of Molecular Virology, Hellenic Pasteur Institute, Athens, Greece.
authors.forename: Urania
authors.initials: U
authors.lastname: Georgopoulou
authors.affiliation: Department of Histology and Embryology, School of Medicine, University of Athens, Athens, Greece.|Biomedical Research Foundation, Academy of Athens, Athens, Greece.|Institute for Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Vassilis G
authors.initials: VG
authors.lastname: Gorgoulis
authors.affiliation: Department of Medicine and Research Laboratory of Internal Medicine, Medical School, University of Thessaly, Larissa, Greece.
authors.forename: George N
authors.initials: GN
authors.lastname: Dalekos
authors.affiliation: Division of Immunology, Biomedical Sciences Research Center Alexander Fleming, Athens, Greece.
authors.forename: Vassilis
authors.identifier: 0000-0001-9531-7729
authors.initials: V
authors.lastname: Aidinis
mesh_terms: D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology*; D001707:Biopsy, Needle; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D002908:Chronic Disease; D004195:Disease Models, Animal; D018450:Disease Progression; D017353:Gene Deletion; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000235:genetics / Q000473:pathology*; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D058990:Molecular Targeted Therapy; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects / Q000235:genetics*; D010879:Piperazines / Q000494:pharmacology*; D000099189:Lysophospholipase D
chemical_list: D001583:Benzoxazoles; D010727:Phosphoric Diester Hydrolases; D010879:Piperazines; D000099189:Lysophospholipase D; C550725:6-(3-(piperazin-1-yl)propanoyl)benzo(d)oxazol-2(3H)-one