Canonical and non-canonical NF-κB signaling promotes breast cancer tumor-initiating cells

M. F. Kendellen, Jennifer Webster Bradford, C. L. Lawrence, K. S. Clark, A. S. Baldwin

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Tumor-initiating cells (TICs) are a sub-population of cells that exhibit a robust ability to self-renew and contribute to the formation of primary tumors, the relapse of previously treated tumors and the development of metastases. TICs have been identified in various tumors including those of the breast, and are particularly enriched in the basal-like and claudin-low subtypes of breast cancer. The signaling pathways that contribute to the function and maintenance of TICs are under intense study. We explored the potential involvement of the nuclear factor-κB (NF-κB) family of transcription factors in TICs in cell lines that are representative of basal-like and claudin-low breast cancer. NF-κB was found to be activated in breast cancer cells that form tumorspheres efficiently. Moreover, both canonical and non-canonical NF-κB signaling is required for these cells to self-renew in vitro and to form xenograft tumors efficiently in vivo using limiting dilutions of cells. Consistent with this fact, canonical and non-canonical NF-κB signaling is activated in TICs isolated from breast cancer cell lines. Experimental results indicate that NF-κB promotes the function of TICs by stimulating epithelial-to-mesenchymal transition and by upregulating the expression of the inflammatory cytokines interleukin-1β and interleukin-6. The results suggest the use of NF-κB inhibitors for clinical therapy of certain breast cancers.

Original languageEnglish (US)
Pages (from-to)1297-1305
Number of pages9
JournalOncogene
Volume33
Issue number10
DOIs
StatePublished - Jan 1 2014

Fingerprint

Neoplastic Stem Cells
Breast Neoplasms
Neoplasms
Cell Line
Epithelial-Mesenchymal Transition
Interleukin-1
Heterografts
Interleukin-6
Breast
Transcription Factors
Maintenance
Cytokines
Neoplasm Metastasis
Recurrence
Population

Keywords

  • EMT
  • IL-1β
  • IL-6
  • NF-κB
  • basal-like breast cancer
  • tumor-initiating cells

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Canonical and non-canonical NF-κB signaling promotes breast cancer tumor-initiating cells. / Kendellen, M. F.; Bradford, Jennifer Webster; Lawrence, C. L.; Clark, K. S.; Baldwin, A. S.

In: Oncogene, Vol. 33, No. 10, 01.01.2014, p. 1297-1305.

Research output: Contribution to journalArticle

Kendellen, M. F. ; Bradford, Jennifer Webster ; Lawrence, C. L. ; Clark, K. S. ; Baldwin, A. S. / Canonical and non-canonical NF-κB signaling promotes breast cancer tumor-initiating cells. In: Oncogene. 2014 ; Vol. 33, No. 10. pp. 1297-1305.
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