Pro-apoptotic Bim suppresses breast tumor cell metastasis and is a target gene of SNAI2
Details
Publication Year 2015-07-23, Volume 34, Issue #30, Page 3926-34
Journal Title
Oncogene
Publication Type
Journal Article
Abstract
Evasion of cell death is fundamental to the development of cancer and its metastasis. The role of the BCL-2-mediated (intrinsic) apoptotic program in these processes remains poorly understood. Here we have investigated the relevance of the pro-apoptotic protein BIM to breast cancer progression using the MMTV-Polyoma middle-T (PyMT) transgenic model. BIM deficiency in PyMT females did not affect primary tumor growth, but substantially increased the survival of metastatic cells within the lung. These data reveal a role for BIM in the suppression of breast cancer metastasis. Intriguingly, we observed a striking correlation between the expression of BIM and the epithelial to mesenchymal transition transcription factor SNAI2 at the proliferative edge of the tumors. Overexpression and knockdown studies confirmed that these two genes were coordinately expressed, and chromatin immunoprecipitation analysis further revealed that Bim is a target of SNAI2. Taken together, our findings suggest that SNAI2-driven BIM-induced apoptosis may temper metastasis by governing the survival of disseminating breast tumor cells.Oncogene advance online publication, 29 September 2014; doi:10.1038/onc.2014.313.
Publisher
NPG
WEHI Research Division(s)
Stem Cells And Cancer; Molecular Genetics Of Cancer
PubMed ID
25263453
NHMRC Grants
NHMRC/637307 NHMRC/1017256
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2014-10-13 02:21:51
Last Modified: 2018-01-16 10:38:43
An error has occurred. This application may no longer respond until reloaded. Reload 🗙