TY - JOUR AB - 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. AD - Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060‑8638, Japan Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Hokkaido 060‑8648, Japan AU - Wakizaka,Kazuki AU - Kamiyama,Toshiya AU - Wakayama,Kenji AU - Orimo,Tatsuya AU - Shimada,Shingo AU - Nagatsu,Akihisa AU - Kamachi,Hirofumi AU - Yokoo,Hideki AU - Fukai,Moto AU - Kobayashi,Nozomi AU - Mitsuhashi,Tomoko AU - Taketomi,Akinobu DA - 2020/11/01 DO - 10.3892/ol.2020.12131 IS - 5 JO - Oncol Lett KW - Wnt5a hepatocellular carcinoma immuno­histochemistry epithelial‑mesenchymal transition PY - 2020 SN - 1792-1074 1792-1082 SP - 268 ST - Role of Wnt5a in suppressing invasiveness of hepatocellular carcinoma via epithelial‑mesenchymal transition T2 - Oncology Letters TI - Role of Wnt5a in suppressing invasiveness of hepatocellular carcinoma via epithelial‑mesenchymal transition UR - https://doi.org/10.3892/ol.2020.12131 VL - 20 ER -