Loss of TBK1 induces epithelial-mesenchymal transition in the breast cancer cells by ERα downregulation

Kyung Min Yang, Yun Shin Jung, Jeong Mi Lee, Won Joo Kim, Jin Ki Cho, Joon Jeong, Seong Jin Kim

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Estrogen receptor α ( ERα) is the pivotal regulator of proliferation and differentiation in mammary epithelia, where it serves as a crucial prognostic marker and therapeutic target in breast cancer. In this study, we show that the loss of the kinase TANK-binding kinase 1 (TBK1) induces epithelial- mesenchymal transition in ERα-positive breast cancer cells by downregulating ERα expression. TBK1 was overexpressed in ERα-positive breast cancers, where it was associated with distant metastasis-free survival in patients, whereas it was underexpressed in ERα-negative breast cancers. TBK1 silencing decreased expression of epithelial markers and increased expression of mesenchymal markers in ERα-positive breast cancer cells, enhancing tumor growth and lung metastasis in vivo in a manner associated with downregulation of ERα expression. Mechanistically, TBK1 silencing reduced FOXO3A binding to the ERα promoter by inducing the translocation of phosphorylated FOXO3A from the nucleus to the cytoplasm. Thus, our results indicate that the loss of TBK1 expression parallels the loss of ERα expression, in turn helping drive an aggressive breast cancer phenotype.

Original languageEnglish
Pages (from-to)6679-6689
Number of pages11
JournalCancer Research
Volume73
Issue number22
DOIs
Publication statusPublished - 2013 Nov 15

Fingerprint

Epithelial-Mesenchymal Transition
Estrogen Receptors
Phosphotransferases
Down-Regulation
Breast Neoplasms
Neoplasm Metastasis
Cytoplasm
Breast
Epithelium
Phenotype
Lung
Survival

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Yang, Kyung Min ; Jung, Yun Shin ; Lee, Jeong Mi ; Kim, Won Joo ; Cho, Jin Ki ; Jeong, Joon ; Kim, Seong Jin. / Loss of TBK1 induces epithelial-mesenchymal transition in the breast cancer cells by ERα downregulation. In: Cancer Research. 2013 ; Vol. 73, No. 22. pp. 6679-6689.
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Loss of TBK1 induces epithelial-mesenchymal transition in the breast cancer cells by ERα downregulation. / Yang, Kyung Min; Jung, Yun Shin; Lee, Jeong Mi; Kim, Won Joo; Cho, Jin Ki; Jeong, Joon; Kim, Seong Jin.

In: Cancer Research, Vol. 73, No. 22, 15.11.2013, p. 6679-6689.

Research output: Contribution to journalArticle

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