{FZD}7 has a critical role in cell proliferation in triple negative breast cancer

  • Yang L
  • Wu X
  • Wang Y
 et al. 
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Breast cancer is genetically and clinically heterogeneous. Triple negative breast cancer ({TNBC}) is a subtype of breast cancer that is usually associated with poor outcome and lack of benefit from targeted therapy. We used microarray analysis to perform a pathway analysis of {TNBC} compared with non-triple negative breast cancer (non-{TNBC}). Overexpression of several Wnt pathway genes, such as frizzled homolog 7 ({FZD}7), low density lipoprotein receptor-related protein 6 and transcription factor 7 ({TCF}7) was observed in {TNBC}, and we directed our focus to the Wnt pathway receptor, {FZD}7. To validate the function of {FZD}7, {FZD}7shRNA was used to knock down {FZD}7 expression. Notably, reduced cell proliferation and suppressed invasiveness and colony formation were observed in {TNBC} {MDA}-{MB}-231 and {BT}-20 cells. Study of the possible mechanism indicated that these effects occurred through silencing of the canonical Wnt signaling pathway, as evidenced by loss of nuclear accumulation of β-catenin and decreased transcriptional activity of {TCF}7. In vivo studies revealed that {FZD}7shRNA significantly suppressed tumor formation, through reduced cell proliferation, in mice bearing xenografts without {FZD}7 expression. Our findings suggest that {FZD}7-involved canonical Wnt signaling pathway is essential for tumorigenesis of {TNBC}, and thus, {FZD}7 shows promise as a biomarker and a potential therapeutic target for {TNBC}.

Author-supplied keywords

  • Breast Neoplasms
  • Cell Line
  • Cell Proliferation
  • Cell Transformation
  • Female
  • Frizzled Receptors
  • Hormone-Dependent
  • Humans
  • Neoplasms
  • Neoplastic
  • Protein Array Analysis
  • Signal Transduction
  • Tumor
  • Up-Regulation
  • Wnt Signaling Pathway

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  • L Yang

  • X Wu

  • Y Wang

  • K Zhang

  • J Wu

  • Y.-C. Yuan

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