Kaiso depletion attenuates the growth and survival of triple negative breast cancer cells

被引:26
作者
Bassey-Archibong, Blessing I. [1 ]
Rayner, Lyndsay G. A. [1 ]
Hercules, Shawn M. [1 ]
Aarts, Craig W. [2 ]
Dvorkin-Gheva, Anna [2 ,3 ]
Bramson, Jonathan L. [2 ]
Hassell, John A. [3 ]
Daniel, Juliet M. [1 ]
机构
[1] McMaster Univ, Dept Biol, LSB-331,1280 Main St West, Hamilton, ON L8S 4K1, Canada
[2] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON L8S 4K1, Canada
[3] McMaster Univ, Dept Biochem & Biomed Sci, Hamilton, ON L8S 4K1, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
MUTANT P53; TRANSCRIPTION FACTOR; CATENIN P120(CTN); MONOCLONAL-ANTIBODIES; MEDIATES SURVIVAL; GENE; MUTATIONS; RESISTANCE; EXPRESSION; BRCA1;
D O I
10.1038/cddis.2017.92
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:e2689 / e2689
页数:11
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