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

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Title: Role of Wnt5a in suppressing invasiveness of hepatocellular carcinoma via epithelial-mesenchymal transition
Authors: Wakizaka, Kazuki Browse this author
Kamiyama, Toshiya Browse this author →KAKEN DB
Wakayama, Kenji Browse this author →KAKEN DB
Orimo, Tatsuya Browse this author →KAKEN DB
Shimada, Shingo Browse this author →KAKEN DB
Nagatsu, Akihisa Browse this author
Kamachi, Hirofumi Browse this author →KAKEN DB
Yokoo, Hideki Browse this author →KAKEN DB
Fukai, Moto Browse this author →KAKEN DB
Kobayashi, Nozomi Browse this author
Mitsuhashi, Tomoko Browse this author →KAKEN DB
Taketomi, Akinobu Browse this author →KAKEN DB
Keywords: Wnt5a
hepatocellular carcinoma
epithelial-mesenchymal transition
Issue Date: Nov-2020
Publisher: Spandidos Publications
Journal Title: Oncology Letters
Volume: 20
Issue: 5
Start Page: 268
Publisher DOI: 10.3892/ol.2020.12131
Abstract: 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.
Type: article
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 脇坂 和貴

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