FOXC1 regulates the functions of human basal-like breast cancer cells by activating NF-κB signaling

J. Wang, P. S. Ray, M. S. Sim, X. Z. Zhou, K. P. Lu, A. V. Lee, X. Lin, S. P. Bagaria, A. E. Giuliano, X. Cui

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Human basal-like breast cancer (BLBC) is an enigmatic and aggressive malignancy with a poor prognosis. There is an urgent need to identify therapeutic targets for BLBC, because current treatment modalities are limited and not effective. The forkhead box transcription factor FOXC1 has recently been identified as a critical functional biomarker for BLBC. However, how it orchestrates BLBC cells was not clear. Here we show that FOXC1 activates the transcription factor nuclear factor-κB (NF-κB) in BLBC cells by increasing p65/RelA protein stability. High NF-κB activity has been associated with estrogen receptor-negative breast cancer, particularly BLBC. The effect of FOXC1 on p65/RelA protein stability is mediated by increased expression of Pin1, a peptidyl-prolyl isomerase. FOXC1 requires NF-κB for its regulation of cell proliferation, migration and invasion. Notably, FOXC1 overexpression renders breast cancer cells more susceptible to pharmacological inhibition of NF-κB. These results suggest that BLBC cells may rely on FOXC1-driven NF-κB signaling. Interventions of this pathway may provide modalities for the treatment of BLBC.

Original languageEnglish (US)
Pages (from-to)4798-4802
Number of pages5
JournalOncogene
Volume31
Issue number45
DOIs
StatePublished - Nov 8 2012
Externally publishedYes

Fingerprint

B-Cell Activating Factor
Breast Neoplasms
Protein Stability
Peptidylprolyl Isomerase
Forkhead Transcription Factors
Estrogen Receptors
Cell Movement
Transcription Factors
Biomarkers

Keywords

  • Basal-like breast cancer
  • FOXC1
  • NF-κB
  • p65/RelA
  • Pin1
  • Protein stability

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Wang, J., Ray, P. S., Sim, M. S., Zhou, X. Z., Lu, K. P., Lee, A. V., ... Cui, X. (2012). FOXC1 regulates the functions of human basal-like breast cancer cells by activating NF-κB signaling. Oncogene, 31(45), 4798-4802. https://doi.org/10.1038/onc.2011.635

FOXC1 regulates the functions of human basal-like breast cancer cells by activating NF-κB signaling. / Wang, J.; Ray, P. S.; Sim, M. S.; Zhou, X. Z.; Lu, K. P.; Lee, A. V.; Lin, X.; Bagaria, S. P.; Giuliano, A. E.; Cui, X.

In: Oncogene, Vol. 31, No. 45, 08.11.2012, p. 4798-4802.

Research output: Contribution to journalArticle

Wang, J, Ray, PS, Sim, MS, Zhou, XZ, Lu, KP, Lee, AV, Lin, X, Bagaria, SP, Giuliano, AE & Cui, X 2012, 'FOXC1 regulates the functions of human basal-like breast cancer cells by activating NF-κB signaling', Oncogene, vol. 31, no. 45, pp. 4798-4802. https://doi.org/10.1038/onc.2011.635
Wang, J. ; Ray, P. S. ; Sim, M. S. ; Zhou, X. Z. ; Lu, K. P. ; Lee, A. V. ; Lin, X. ; Bagaria, S. P. ; Giuliano, A. E. ; Cui, X. / FOXC1 regulates the functions of human basal-like breast cancer cells by activating NF-κB signaling. In: Oncogene. 2012 ; Vol. 31, No. 45. pp. 4798-4802.
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