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 |
metastasis |
prognosis |
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. |
http://creativecommons.org/licenses/by/4.0/ |
Type: | article |
URI: | http://hdl.handle.net/2115/66651 |
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)
|