Down-regulation of Frizzled-7 expression inhibits migration, invasion, and epithelial–mesenchymal transition of cervical cancer cell lines

• Published in: Medical oncology (Northwood, London, England) London, England), 2015-04, Vol.32 (4), p.102-102, Article 102
• Main Authors: Deng, Boya, Zhang, Siyang, Miao, Yuan, Zhang, Yi, Wen, Fang, Guo, Kejun
• Format: Article
• Language: English
• Subjects: Apoptosis; Blotting, Western; Cadherins - genetics; Cadherins - metabolism; Cell Movement; Cell Proliferation; Cervical cancer; Epithelial-Mesenchymal Transition; Female; Fluorescent Antibody Technique; Frizzled Receptors - antagonists & inhibitors; Frizzled Receptors - genetics; Frizzled Receptors - metabolism; Gene Expression Regulation, Neoplastic; Hematology; Humans; Internal Medicine; Medicine; Medicine & Public Health; Neoplasm Invasiveness; Oncology; Original Paper; Pathology; Phosphorylation; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Small Interfering - genetics; Signal Transduction; Tumor Cells, Cultured; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - pathology
• ISSN: 1357-0560; 1559-131X
• DOI: 10.1007/s12032-015-0552-8

Frizzled-7 (FZD7) has been demonstrated as a critical receptor of the Wnt signaling and involves in tumorigenesis and metastasis in many cancer types. However, limited information was found in cervical cancer. The aim of this study was to investigate the functional role of FZD7 in migration, invasion, and epithelial–mesenchymal transition (EMT) of cervical cancer cells. HeLa and SiHa cervical carcinoma cell lines with FZD7 expression were chosen in this study. A short hairpin RNA (shRNA) construct targeting FZD7 mRNA was transfected into HeLa and SiHa cells, and the stably transfected cell lines were obtained through G418 screening. Functional experiments were further performed to assess whether FZD7 down-regulation affects the migration, invasion, and EMT of HeLa and SiHa cells. Our results revealed that down-regulation of FZD7 expression significantly inhibited cell invasion and migration, as well as decreased the expression and activities of MMP2 and MMP9 in both cell types. Additionally, FZD7 silencing resulted in down-regulation of mesenchymal markers including Vimentin and Snail while increased the levels of epithelial marker E-cadherin. We further found that decreased FZD7 expression inhibited the phosphorylation levels of JNK and c-jun in both HeLa and SiHa cells, as determined by Western blot analysis and immunofluorescence. Overall, our results indicate that shRNA-mediated knockdown of FZD7 inhibits invasion, metastasis, and EMT of cervical cancer cells. FZD7 may provide a promising therapeutic target in cervical cancer.