Pro-apoptotic Bim suppresses breast tumor cell metastasis and is a target gene of SNAI2

Delphine Merino, Sarah A Best, Marie-Liesse Asselin-Labat, Francois Vaillant, Bhupinder Pal, Ross Alexander Dickins, Robin L Anderson, Andreas Strasser, Phillipe Bouillet, Geoffery J Lindeman, Jane Visvader

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23 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)3926 - 3934
Number of pages9
JournalOncogene
Volume34
Issue number30
DOIs
Publication statusPublished - 2015
Externally publishedYes

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