Kaiso depletion attenuates the growth and survival of triple negative breast cancer cells.
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.
Department of Biology, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
Blessing I
BI
Bassey-Archibong
Department of Biology, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
Lyndsay G A
LG
Rayner
Department of Biology, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
Shawn M
SM
Hercules
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
Craig W
CW
Aarts
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8S 4K1, Canada.|Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
Anna
A
Dvorkin-Gheva
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
Jonathan L
JL
Bramson
Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
John A
JA
Hassell
Department of Biology, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
Juliet M
JM
Daniel
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D019313:BRCA1 Protein / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014157:Transcription Factors / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D016159:Tumor Suppressor Protein p53
D019313:BRCA1 Protein; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C492254:ZBTB33 protein, human