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

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 .