Role of Wnt5a in suppressing invasiveness of hepatocellular carcinoma via epithelial-mesenchymal transition

Wakizaka, Kazuki; Kamiyama, Toshiya; Wakayama, Kenji et al.

Oncology Letters, 2020, 20(5), 268

Permalink : https://hdl.handle.net/2115/82493

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アクセス権
open access
URI
https://hdl.handle.net/2115/82493
タイトル
Role of Wnt5a in suppressing invasiveness of hepatocellular carcinoma via epithelial-mesenchymal transition
著者
Wakizaka, Kazuki ; Kamiyama, Toshiya ; Wakayama, Kenji ; Orimo, Tatsuya ; Shimada, Shingo ; Nagatsu, Akihisa ; Kamachi, Hirofumi ; Yokoo, Hideki ; Fukai, Moto ; Kobayashi, Nozomi ; Mitsuhashi, Tomoko ; Taketomi, Akinobu
著者名
Wakizaka, Kazuki
e-Rad_Researcher
80322816
著者名
Kamiyama, Toshiya
e-Rad_Researcher
50646544
著者名
Wakayama, Kenji
e-Rad_Researcher
80711861
著者名
Orimo, Tatsuya
e-Rad_Researcher
40755576
著者名
Shimada, Shingo
著者名
Nagatsu, Akihisa
e-Rad_Researcher
60374237
著者名
Kamachi, Hirofumi
e-Rad_Researcher
70399947
著者名
Yokoo, Hideki
e-Rad_Researcher
60374344
著者名
Fukai, Moto
著者名
Kobayashi, Nozomi
e-Rad_Researcher
60348208
著者名
Mitsuhashi, Tomoko
e-Rad_Researcher
70363364
著者名
Taketomi, Akinobu
言語
英語
キーワード
Wnt5a
hepatocellular carcinoma
immunohistochemistry
epithelial-mesenchymal transition
発行日
2020-11
出版者
Spandidos Publications
収録物名
Oncology Letters
巻(号)
20(5)
ページ
268
抄録
Inappropriate activation of the canonical Wnt signaling pathway is associated with progression of hepatocellular carcinoma (HCC). However, the association between the non-canonical pathway activated by Wnt5a and HCC is not well known. The present study investigated the significance of Wnt5a expression in HCC. Immunohistochemical staining of Wnt5a was performed on specimens from 243 patients who underwent hepatic resection for HCC. The present study investigated whether Wnt5a expression was associated with clinical and pathological factors and prognosis. Wnt5a expression in human HCC cell lines was investigated using western blotting. The effects of overexpression or knockdown of Wnt5a were evaluated using proliferation and invasion assays. Changes in epithelial-mesenchymal transition (EMT)-related molecules were investigated using western blotting. Wnt5a negativity was significantly associated with poor tumor differentiation and positive vascular invasion. In univariate analysis, Wnt5a negativity was identified as a significant prognostic factor for overall survival (OS). Multivariate analysis of OS demonstrated that Wnt5a negativity was an independent prognostic factor. Wnt5a expression was lower in HLE and HLF cells than in HepG2 and Huh7 cells. Knockdown of Wnt5a by short hairpin RNA transfection increased the proliferation and invasiveness of Huh7 cells, and decreased the expression levels of E-cadherin. In HLF cells, overexpression of Wnt5a inhibited invasiveness and decreased the expression levels of vimentin. Wnt5a negativity was associated with poor tumor differentiation and positive vascular invasion, and was an independent poor prognostic factor in patients with HCC. Wnt5a may be a tumor suppressor involved in EMT-mediated changes in invasiveness.
資源タイプ
学術雑誌論文
出版タイプ
Version of Record
PISSN
1792-1074
関連情報 (isIdenticalTo)
出版社版DOI
https://doi.org/10.3892/ol.2020.12131