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
(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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https://lup.lub.lu.se/record/4272353
- author
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- 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
- pmid:23955085
- ISSN
- 1476-5594
- DOI
- 10.1038/onc.2013.322
- language
- English
- LU publication?
- yes
- id
- b4402852-90f5-4d50-950c-ea3699c6f376 (old id 4272353)
- date added to LUP
- 2016-04-01 09:52:38
- date last changed
- 2022-02-02 03:43:40
@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}}, keywords = {{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}}, doi = {{10.1038/onc.2013.322}}, volume = {{32}}, year = {{2013}}, }