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

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Abstract

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.

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Acknowledgments

This study was supported by a Grant from The First Affiliated Hospital of China Medical University (No. FSFH1214).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Gynecology, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, People’s Republic of China

    Boya Deng, Yi Zhang, Fang Wen & Kejun Guo

  2. Central Laboratory, China Medical University, Shenyang, 110001, People’s Republic of China

    Siyang Zhang

  3. Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, 110001, People’s Republic of China

    Yuan Miao

Authors
  1. Boya Deng
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  2. Siyang Zhang
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  3. Yuan Miao
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  4. Yi Zhang
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  5. Fang Wen
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  6. Kejun Guo
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Correspondence to Boya Deng.

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Deng, B., Zhang, S., Miao, Y. et al. Down-regulation of Frizzled-7 expression inhibits migration, invasion, and epithelial–mesenchymal transition of cervical cancer cell lines. Med Oncol 32, 102 (2015). https://doi.org/10.1007/s12032-015-0552-8

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