title: Fatty acid-binding protein 5 function in hepatocellular carcinoma through induction of epithelial-mesenchymal transition.
abstract: Hepatocellular carcinoma (HCC) is a highly prevalent cancer with poor prognosis. The correlation between overexpression of fatty acid-binding protein 5 (FABP5) and malignant potential of tumor growth and metastasis in several cancers has been previously reported. However, the correlation between FABP5 expression and HCC malignant behavior remains unknown. We compared FABP5 expression and patient characteristics in paired HCC and adjacent noncancerous liver tissues from 243 patients who underwent surgical resection of primary HCC. Cell proliferation, invasion, and migration assays were performed in HCC cell lines overexpressing FABP5 or downregulated for FABP5. Tumor growths were monitored in xenograft model, and liver and lung metastasis models were established. In the 243 HCC patients, FABP5-positive staining (n = 139/243, 57.2%) was associated with poor prognosis and recurrence (P < 0.0001) and showed positive correlation with distant metastasis, tumor size and vascular invasion (P < 0.05). Cell proliferation, invasion, and migration in vitro were enhanced by upregulation of FABP5 and decreased by downregulation of FABP5 in HCC cell lines. Similar results in tumor formation and metastasis were obtained through in vivo analyses. PCR array results revealed upregulation of SNAI1 in FABP5-overexpressing HepG2 cells. Western blot analysis showed significantly increased expression of E-cadherin and ZO-1 and decreased SNAI1 expression and nuclear translocation of β-catenin by knockdown of FABP5. We revealed a significant role for FABP5 in HCC progression and metastasis through the induction of epithelial-to-mesenchymal transition. FABP5 may be a potential novel prognostic biomarker and new therapeutic target for HCC.
authors.affiliation: Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Takanori
authors.identifier: http://orcid.org/0000-0003-1994-5349
authors.initials: T
authors.lastname: Ohata
authors.affiliation: Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Yokoo
authors.affiliation: Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Kamiyama
authors.affiliation: Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Moto
authors.initials: M
authors.lastname: Fukai
authors.affiliation: Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Aiyama
authors.affiliation: Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hatanaka
authors.affiliation: Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Hatanaka
authors.affiliation: Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Wakayama
authors.affiliation: Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Orimo
authors.affiliation: Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kakisaka
authors.affiliation: Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Kobayashi
authors.affiliation: Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsuno
authors.affiliation: Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Akinobu
authors.initials: A
authors.lastname: Taketomi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D050556:Fatty Acid-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation
chemical_list: C493412:FABP5 protein, human; D050556:Fatty Acid-Binding Proteins
keywords: Epithelial-mesenchymal transition; fatty acid-binding protein; hepatocellular carcinoma; metastasis; prognosis