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MiR-155-mediated loss of C/EBP beta shifts the TGF-beta response from growth inhibition to epithelial-mesenchymal transition, invasion and metastasis in breast cancer

Johansson, J.; Berg, T.; Kurzejamska, E.; Pang, M-F; Tabor, V.; Jansson, M.; Roswall, P.; Pietras, Kristian LU ; Sund, M. and Religa, P., et al. (2013) In Oncogene 32(50). p.5614-5624
Abstract
During breast cancer progression, transforming growth factor-beta (TGF-beta) switches from acting as a growth inhibitor to become a major promoter of epithelial-mesenchymal transition (EMT), invasion and metastasis. However, the mechanisms involved in this switch are not clear. We found that loss of CCAAT-enhancer binding protein beta (C/EBP beta), a differentiation factor for the mammary epithelium, was associated with signs of EMT in triple-negative human breast cancer, and in invasive areas of mammary tumors in MMTV-PyMT mice. Using an established model of TGF-beta-induced EMT in mouse mammary gland epithelial cells, we discovered that C/EBP beta was repressed during EMT by miR-155, an oncomiR in breast cancer. Depletion of C/EBP beta... (More)
During breast cancer progression, transforming growth factor-beta (TGF-beta) switches from acting as a growth inhibitor to become a major promoter of epithelial-mesenchymal transition (EMT), invasion and metastasis. However, the mechanisms involved in this switch are not clear. We found that loss of CCAAT-enhancer binding protein beta (C/EBP beta), a differentiation factor for the mammary epithelium, was associated with signs of EMT in triple-negative human breast cancer, and in invasive areas of mammary tumors in MMTV-PyMT mice. Using an established model of TGF-beta-induced EMT in mouse mammary gland epithelial cells, we discovered that C/EBP beta was repressed during EMT by miR-155, an oncomiR in breast cancer. Depletion of C/EBP beta potentiated the TGF-beta response towards EMT, and contributed to evasion of the growth inhibitory response to TGF-beta. Furthermore, loss of C/EBP beta enhanced invasion and metastatic dissemination of the mouse mammary tumor cells to the lungs after subcutaneous injection into mice. The mechanism by which loss of C/EBP beta promoted the TGF-beta response towards EMT, invasion and metastasis, was traced to a previously uncharacterized role of C/EBP beta as a transcriptional activator of genes encoding the epithelial junction proteins E-cadherin and coxsackie virus and adenovirus receptor. The results identify miR-155-mediated loss of C/EBP beta as a mechanism, which promotes breast cancer progression by shifting the TGF-beta response from growth inhibition to EMT, invasion and metastasis. (Less)
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keywords
CCAAT-enhancer binding protein beta, epithelial-mesenchymal transition, transforming growth factor-beta, Breast cancer, metastasis
in
Oncogene
volume
32
issue
50
pages
5614 - 5624
publisher
Nature Publishing Group
external identifiers
  • wos:000328461400006
  • scopus:84890572219
ISSN
1476-5594
DOI
10.1038/onc.2013.322
language
English
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yes
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b4402852-90f5-4d50-950c-ea3699c6f376 (old id 4272353)
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2014-02-10 12:19:22
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2019-09-17 01:02:58
@article{b4402852-90f5-4d50-950c-ea3699c6f376,
  abstract     = {During breast cancer progression, transforming growth factor-beta (TGF-beta) switches from acting as a growth inhibitor to become a major promoter of epithelial-mesenchymal transition (EMT), invasion and metastasis. However, the mechanisms involved in this switch are not clear. We found that loss of CCAAT-enhancer binding protein beta (C/EBP beta), a differentiation factor for the mammary epithelium, was associated with signs of EMT in triple-negative human breast cancer, and in invasive areas of mammary tumors in MMTV-PyMT mice. Using an established model of TGF-beta-induced EMT in mouse mammary gland epithelial cells, we discovered that C/EBP beta was repressed during EMT by miR-155, an oncomiR in breast cancer. Depletion of C/EBP beta potentiated the TGF-beta response towards EMT, and contributed to evasion of the growth inhibitory response to TGF-beta. Furthermore, loss of C/EBP beta enhanced invasion and metastatic dissemination of the mouse mammary tumor cells to the lungs after subcutaneous injection into mice. The mechanism by which loss of C/EBP beta promoted the TGF-beta response towards EMT, invasion and metastasis, was traced to a previously uncharacterized role of C/EBP beta as a transcriptional activator of genes encoding the epithelial junction proteins E-cadherin and coxsackie virus and adenovirus receptor. The results identify miR-155-mediated loss of C/EBP beta as a mechanism, which promotes breast cancer progression by shifting the TGF-beta response from growth inhibition to EMT, invasion and metastasis.},
  author       = {Johansson, J. and Berg, T. and Kurzejamska, E. and Pang, M-F and Tabor, V. and Jansson, M. and Roswall, P. and Pietras, Kristian and Sund, M. and Religa, P. and Fuxe, J.},
  issn         = {1476-5594},
  keyword      = {CCAAT-enhancer binding protein beta,epithelial-mesenchymal transition,transforming growth factor-beta,Breast cancer,metastasis},
  language     = {eng},
  number       = {50},
  pages        = {5614--5624},
  publisher    = {Nature Publishing Group},
  series       = {Oncogene},
  title        = {MiR-155-mediated loss of C/EBP beta shifts the TGF-beta response from growth inhibition to epithelial-mesenchymal transition, invasion and metastasis in breast cancer},
  url          = {http://dx.doi.org/10.1038/onc.2013.322},
  volume       = {32},
  year         = {2013},
}