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Identification of a cancer stem cell-specific function for the histone
deacetylases, HDAC1 and HDAC7, in breast and ovarian cancer
#MMPMID27694895
Witt AE
; Lee CW
; Lee TI
; Azzam DJ
; Wang B
; Caslini C
; Petrocca F
; Grosso J
; Jones M
; Cohick EB
; Gropper AB
; Wahlestedt C
; Richardson AL
; Shiekhattar R
; Young RA
; Ince TA
Oncogene
2017[Mar]; 36
(12
): 1707-1720
PMID27694895
show ga
Tumours are comprised of a highly heterogeneous population of cells, of which
only a small subset of stem-like cells possess the ability to regenerate tumours
in vivo. These cancer stem cells (CSCs) represent a significant clinical
challenge as they are resistant to conventional cancer therapies and play
essential roles in metastasis and tumour relapse. Despite this realization and
great interest in CSCs, it has been difficult to develop CSC-targeted treatments
due to our limited understanding of CSC biology. Here, we present evidence that
specific histone deacetylases (HDACs) play essential roles in the CSC phenotype.
Utilizing a novel CSC model, we discovered that the HDACs, HDAC1 and HDAC7, are
specifically over-expressed in CSCs when compared to non-stem-tumour-cells
(nsTCs). Furthermore, we determine that HDAC1 and HDAC7 are necessary to maintain
CSCs, and that over-expression of HDAC7 is sufficient to augment the CSC
phenotype. We also demonstrate that clinically available HDAC inhibitors (HDACi)
targeting HDAC1 and HDAC7 can be used to preferentially target CSCs. These
results provide actionable insights that can be rapidly translated into
CSC-specific therapies.
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