1. Kaiso depletion attenuates the growth and survival of triple negative breast cancer cells.
- Author
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Bassey-Archibong BI, Rayner LG, Hercules SM, Aarts CW, Dvorkin-Gheva A, Bramson JL, Hassell JA, and Daniel JM
- Subjects
- Animals, Apoptosis physiology, BRCA1 Protein metabolism, Cell Line, Tumor, Female, Humans, MCF-7 Cells, Mice, Mice, Inbred NOD, Mice, SCID, Tumor Suppressor Protein p53, Cell Proliferation physiology, Transcription Factors metabolism, Triple Negative Breast Neoplasms metabolism, Triple Negative Breast Neoplasms pathology
- Abstract
Triple negative breast cancers (TNBC) are highly aggressive and lack specific targeted therapies. Recent studies have reported high expression of the transcription factor Kaiso in triple negative tumors, and this correlates with their increased aggressiveness. However, little is known about the clinical relevance of Kaiso in the growth and survival of TNBCs. Herein, we report that Kaiso depletion attenuates TNBC cell proliferation, and delays tumor onset in mice xenografted with the aggressive MDA-231 breast tumor cells. We further demonstrate that Kaiso depletion attenuates the survival of TNBC cells and increases their propensity for apoptotic-mediated cell death. Notably, Kaiso depletion downregulates BRCA1 expression in TNBC cells expressing mutant-p53 and we found that high Kaiso and BRCA1 expression correlates with a poor overall survival in breast cancer patients. Collectively, our findings reveal a role for Kaiso in the proliferation and survival of TNBC cells, and suggest a relevant role for Kaiso in the prognosis and treatment of TNBCs.
- Published
- 2017
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