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

2017; Wiley; Volume: 6; Issue: 5 Linguagem: Inglês

10.1002/cam4.1020

2045-7634

Takanori Ohata, Hideki Yokoo, Toshiya Kamiyama, Moto Fukai, Takeshi Aiyama, Yutaka Hatanaka, Kanako C. Hatanaka, Kenji Wakayama, Tatsuya Orimo, Tatsuhiko Kakisaka, Nozomi Kobayashi, Yoshihiro Matsuno, Akinobu Taketomi,

Drug Transport and Resistance Mechanisms

Abstract Hepatocellular carcinoma ( HCC ) is a highly prevalent cancer with poor prognosis. The correlation between overexpression of fatty acid‐binding protein 5 ( FABP 5) and malignant potential of tumor growth and metastasis in several cancers has been previously reported. However, the correlation between FABP 5 expression and HCC malignant behavior remains unknown. We compared FABP 5 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 FABP 5 or downregulated for FABP 5. Tumor growths were monitored in xenograft model, and liver and lung metastasis models were established. In the 243 HCC patients, FABP 5‐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 FABP 5 and decreased by downregulation of FABP 5 in HCC cell lines. Similar results in tumor formation and metastasis were obtained through in vivo analyses. PCR array results revealed upregulation of SNAI 1 in FABP 5‐overexpressing HepG2 cells. Western blot analysis showed significantly increased expression of E‐cadherin and ZO ‐1 and decreased SNAI 1 expression and nuclear translocation of β ‐catenin by knockdown of FABP 5. We revealed a significant role for FABP 5 in HCC progression and metastasis through the induction of epithelial‐to‐mesenchymal transition. FABP 5 may be a potential novel prognostic biomarker and new therapeutic target for HCC .