NF-κΒ is essential for epithelial- mesenchymal transition and metastasis in a model of breast cancer progression.
In: Journal of Clinical Investigation, Jg. 114 (2004-08-15), Heft 4, S. 569-581
academicJournal
Zugriff:
The transcription factor NF-κB is activated in a range of human cancers and is thought to promote tumorigenesis, mainly due to its ability to protect transformed cells from apoptosis. To investigate the role of NF-κB in epithelial plasticity and metastasis, we utilized a well-characterized in vitro/in vivo model of mammary carcinogenesis that depends on the collaboration of the Ha-Ras oncoprotein and TGF-β. We show here that the IKK-2/IκBct/NF-κB pathway is required for the induction and maintenance of epithelial-mesenchymal transition (EMT). Inhibition of NF-κB signaling prevented EMT in Ras-transformed epithelial cells, while activation of this pathway promoted the transition to a mesenchymal phenotype even in the absence of TGF-β. Furthermore, inhibition of NF-κB activity in mesenchymal cells caused a reversal of EMT, suggesting that NF-κB is essential for both the induction and maintenance of EMT. In line with the importance of EMT for invasion, blocking of NF-κB activity abrogated the metastatic potential of mammary epithelial cells in a mouse model system. Collectively, these data provide evidence of an essential role for NF-κB during distinct steps of breast cancer progression and suggest that the cooperation of Ras- and TGF-β-dependent signaling pathways in late-stage tumorigenesis depends critically on NF-κB activity. [ABSTRACT FROM AUTHOR]
Titel: |
NF-κΒ is essential for epithelial- mesenchymal transition and metastasis in a model of breast cancer progression.
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Autor/in / Beteiligte Person: | Huber, Margit A. ; Azoitei, Ninel ; Baumann, Bernd ; Grünert, Stefan ; Sommer, Andreas ; Pehamberger, Hubert ; Kraut, Norbert ; Beug, Hartmut ; Wirth, Thomas |
Zeitschrift: | Journal of Clinical Investigation, Jg. 114 (2004-08-15), Heft 4, S. 569-581 |
Veröffentlichung: | 2004 |
Medientyp: | academicJournal |
ISSN: | 0021-9738 (print) |
DOI: | 10.1172/JCI200421358 |
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