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2017 ; 6
(5
): 1049-1061
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Fatty acid-binding protein 5 function in hepatocellular carcinoma through
induction of epithelial-mesenchymal transition
#MMPMID28374947
Ohata T
; Yokoo H
; Kamiyama T
; Fukai M
; Aiyama T
; Hatanaka Y
; Hatanaka K
; Wakayama K
; Orimo T
; Kakisaka T
; Kobayashi N
; Matsuno Y
; Taketomi A
Cancer Med
2017[May]; 6
(5
): 1049-1061
PMID28374947
show ga
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 ?-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.
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