title: Wnt5a promotes vasculogenic mimicry and epithelial-mesenchymal transition via protein kinase Cα in epithelial ovarian cancer.
abstract: Epithelial ovarian cancer is one of the most common causes of cancer-related death in women. The majority of epithelial ovarian cancer patients present with metastasis at the time of initial diagnosis. Studies have demonstrated that vasculogenic mimicry (VM) is highly correlated with metastasis and invasiveness, and epithelial-mesenchymal transition (EMT) is pivotal in VM formation. Wnt5a, a member of the Wnt protein family, can activate the non-canonical Wnt signaling pathway mediating cancer initiation and progression. Thus, the present study aimed to investigate the relationship between Wnt5a and VM and its mechanism in epithelial ovarian cancer. The present results showed that Wnt5a staining was significantly correlated with metastasis in epithelial ovarian cancer. The correlation between the expression of Wnt5a and VM or protein kinase Cα (PKCα) indicated that Wnt5a was associated with VM and may be linked to the PKC pathway. In vitro experiments revealed that Wnt5a enhanced the vasculogenic capacity, motility and invasiveness of ovarian cancer cells; however, the PKCα inhibitor blocked these effects. Western blot analysis showed that changes in Wnt5a expression coincided with changes in PKC expression and that PI3K and Snail expression increased along with Wnt5a upregulation. However, no change was observed in β-catenin levels, indicating that Wnt5a may mediate EMT and VM in ovarian cancer cells via the PKCα pathway.
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300070, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Qi
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300070, P.R. China.
authors.forename: Baocun
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300070, P.R. China.
authors.forename: Xiulan
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300070, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300070, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gu
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300070, P.R. China.
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300070, P.R. China.
authors.forename: Runfen
authors.initials: R
authors.lastname: Cheng
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300070, P.R. China.
authors.forename: Xueyi
authors.initials: X
authors.lastname: Dong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000473:pathology; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*; D000071818:Wnt-5a Protein; D055815:Young Adult
chemical_list: D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C496628:PRKCA protein, human; D051571:Protein Kinase C-alpha