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 language | English |
|---|---|
| Pages (from-to) | 6679-6689 |
| Number of pages | 11 |
| Journal | Cancer Research |
| Volume | 73 |
| Issue number | 22 |
| DOIs | |
| Publication status | Published - 2013 Nov 15 |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
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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 journal › Article
TY - JOUR
T1 - Loss of TBK1 induces epithelial-mesenchymal transition in the breast cancer cells by ERα downregulation
AU - Yang, Kyung Min
AU - Jung, Yun Shin
AU - Lee, Jeong Mi
AU - Kim, Won Joo
AU - Cho, Jin Ki
AU - Jeong, Joon
AU - Kim, Seong Jin
PY - 2013/11/15
Y1 - 2013/11/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84888349028&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84888349028&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-13-0891
DO - 10.1158/0008-5472.CAN-13-0891
M3 - Article
C2 - 24062311
AN - SCOPUS:84888349028
VL - 73
SP - 6679
EP - 6689
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 22
ER -