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Kristian Pietras

Kristian Pietras

Research team manager

Kristian Pietras

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

Author

  • J. Johansson
  • T. Berg
  • E. Kurzejamska
  • M-F Pang
  • V. Tabor
  • M. Jansson
  • P. Roswall
  • Kristian Pietras
  • M. Sund
  • P. Religa
  • J. Fuxe
Show all

Summary, in English

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.

Department/s

  • Division of Translational Cancer Research

Publishing year

2013

Language

English

Pages

5614-5624

Publication/Series

Oncogene

Volume

32

Issue

50

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Cancer and Oncology

Keywords

  • CCAAT-enhancer binding protein beta
  • epithelial-mesenchymal transition
  • transforming growth factor-beta
  • Breast cancer
  • metastasis

Status

Published

ISBN/ISSN/Other

  • ISSN: 1476-5594