FZD7 has a critical role in cell proliferation in triple negative breast cancer

L. Yang, X. Wu, Y. Wang, K. Zhang, J. Wu, Y. C. Yuan, X. Deng, L. Chen, C. C.H. Kim, S. Lau, G. Somlo, Y. Yen

Research output: Contribution to journalArticle

153 Citations (Scopus)

Abstract

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 (FZD7), low density lipoprotein receptor-related protein 6 and transcription factor 7 (TCF7) was observed in TNBC, and we directed our focus to the Wnt pathway receptor, FZD7. To validate the function of FZD7, FZD7shRNA was used to knock down FZD7 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 TCF7. In vivo studies revealed that FZD7shRNA significantly suppressed tumor formation, through reduced cell proliferation, in mice bearing xenografts without FZD7 expression. Our findings suggest that FZD7-involved canonical Wnt signaling pathway is essential for tumorigenesis of TNBC, and thus, FZD7 shows promise as a biomarker and a potential therapeutic target for TNBC.

Original languageEnglish
Pages (from-to)4437-4446
Number of pages10
JournalOncogene
Volume30
Issue number43
DOIs
Publication statusPublished - Oct 27 2011
Externally publishedYes

Fingerprint

Triple Negative Breast Neoplasms
Wnt Signaling Pathway
Cell Proliferation
T Cell Transcription Factor 1
Breast Neoplasms
Low Density Lipoprotein Receptor-Related Protein-6
Wnt Receptors
Catenins
Microarray Analysis
Heterografts
Carcinogenesis
Biomarkers
Therapeutics
Genes

Keywords

  • FZD7
  • potential therapeutic target
  • proliferation
  • TNBC
  • Wnt canonical signaling pathway

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

FZD7 has a critical role in cell proliferation in triple negative breast cancer. / Yang, L.; Wu, X.; Wang, Y.; Zhang, K.; Wu, J.; Yuan, Y. C.; Deng, X.; Chen, L.; Kim, C. C.H.; Lau, S.; Somlo, G.; Yen, Y.

In: Oncogene, Vol. 30, No. 43, 27.10.2011, p. 4437-4446.

Research output: Contribution to journalArticle

Yang, L, Wu, X, Wang, Y, Zhang, K, Wu, J, Yuan, YC, Deng, X, Chen, L, Kim, CCH, Lau, S, Somlo, G & Yen, Y 2011, 'FZD7 has a critical role in cell proliferation in triple negative breast cancer', Oncogene, vol. 30, no. 43, pp. 4437-4446. https://doi.org/10.1038/onc.2011.145
Yang L, Wu X, Wang Y, Zhang K, Wu J, Yuan YC et al. FZD7 has a critical role in cell proliferation in triple negative breast cancer. Oncogene. 2011 Oct 27;30(43):4437-4446. https://doi.org/10.1038/onc.2011.145
Yang, L. ; Wu, X. ; Wang, Y. ; Zhang, K. ; Wu, J. ; Yuan, Y. C. ; Deng, X. ; Chen, L. ; Kim, C. C.H. ; Lau, S. ; Somlo, G. ; Yen, Y. / FZD7 has a critical role in cell proliferation in triple negative breast cancer. In: Oncogene. 2011 ; Vol. 30, No. 43. pp. 4437-4446.
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