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Fatty acid-binding protein 5 function in hepatocellular carcinoma through induction of epithelial-mesenchymal transition

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Title: Fatty acid-binding protein 5 function in hepatocellular carcinoma through induction of epithelial-mesenchymal transition
Authors: Ohata, Takanori Browse this author
Yokoo, Hideki Browse this author →KAKEN DB
Kamiyama, Toshiya Browse this author →KAKEN DB
Fukai, Moto Browse this author →KAKEN DB
Aiyama, Takeshi Browse this author
Hatanaka, Yutaka Browse this author →KAKEN DB
Hatanaka, Kanako Browse this author
Wakayama, Kenji Browse this author
Orimo, Tatsuya Browse this author
Kakisaka, Tatsuhiko Browse this author →KAKEN DB
Kobayashi, Nozomi Browse this author
Matsuno, Yoshihiro Browse this author →KAKEN DB
Taketomi, Akinobu Browse this author →KAKEN DB
Keywords: Epithelial-mesenchymal transition
fatty acid-binding protein
hepatocellular carcinoma
Issue Date: May-2017
Publisher: John Wiley & Sons
Journal Title: Cancer medicine
Volume: 6
Issue: 5
Start Page: 1049
End Page: 1061
Publisher DOI: 10.1002/cam4.1020
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 beta-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.
Rights: Fatty acid-binding protein 5 function in hepatocellular carcinoma through induction of epithelial–mesenchymal, Takanori Ohata, Hideki Yokoo, Toshiya Kamiyama, Moto Fukai, Takeshi Aiyama, Yutaka Hatanaka, Kanako Hatanaka, Kenji Wakayama, Tatsuya Orimo, Tatsuhiko Kakisaka, Nozomi Kobayashi, Yoshihiro Matsuno & Akinobu Taketomi, Cancer Medicine, 6(5). Copyright (c) 2017 The Authors.
Type: article
Appears in Collections:北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 横尾 英樹

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