PMID- 23024790
OWN - NLM
STAT- MEDLINE
DCOM- 20130215
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 9
DP  - 2012
TI  - Histone deacetylase inhibitors induce epithelial-to-mesenchymal transition in 
      prostate cancer cells.
PG  - e45045
LID - e45045
AB  - Clinical experience of histone deacetylase inhibitors (HDACIs) in patients with 
      solid tumors has been disappointing; however, the molecular mechanism of 
      treatment failure is not known. Therefore, we sought to investigate the molecular 
      mechanism of treatment failure of HDACIs in the present study. We found that 
      HDACIs Trichostatin A (TSA) and Suberoylanilide hydroxamic acid (SAHA) could 
      induce epithelial-to-mesenchymal transition (EMT) phenotype in prostate cancer 
      (PCa) cells, which was associated with changes in cellular morphology consistent 
      with increased expression of transcription factors ZEB1, ZEB2 and Slug, and 
      mesenchymal markers such as vimentin, N-cadherin and Fibronectin. CHIP assay 
      showed acetylation of histone 3 on proximal promoters of selected genes, which 
      was in part responsible for increased expression of EMT markers. Moreover, TSA 
      treatment led to further increase in the expression of Sox2 and Nanog in PCa 
      cells with EMT phenotype, which was associated with cancer stem-like cell (CSLC) 
      characteristics consistent with increased cell motility. Our results suggest that 
      HDACIs alone would lead to tumor aggressiveness, and thus strategies for 
      reverting EMT-phenotype to mesenchymal-to-epithelial transition (MET) phenotype 
      or the reversal of CSLC characteristics prior to the use of HDACIs would be 
      beneficial to realize the value of HDACIs for the treatment of solid tumors 
      especially PCa.
FAU - Kong, Dejuan
AU  - Kong D
AD  - Department of Pathology, Karmanos Cancer Institute, Wayne State University School 
      of Medicine, Detroit, Michigan, United States of America.
FAU - Ahmad, Aamir
AU  - Ahmad A
FAU - Bao, Bin
AU  - Bao B
FAU - Li, Yiwei
AU  - Li Y
FAU - Banerjee, Sanjeev
AU  - Banerjee S
FAU - Sarkar, Fazlul H
AU  - Sarkar FH
LA  - eng
GR  - R01 CA083695/CA/NCI NIH HHS/United States
GR  - R01 CA108535/CA/NCI NIH HHS/United States
GR  - 5R01CA083695-09/CA/NCI NIH HHS/United States
GR  - 5R01CA108535-06/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120914
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Biomarkers)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Histones)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Acetylation
MH  - Biomarkers/metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects/genetics
MH  - Epithelial-Mesenchymal Transition/*drug effects/genetics
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Histone Deacetylase Inhibitors/*pharmacology
MH  - Histones/metabolism
MH  - Humans
MH  - Male
MH  - Neoplastic Stem Cells/drug effects/metabolism
MH  - Phenotype
MH  - Promoter Regions, Genetic
MH  - Prostatic Neoplasms/*genetics/*metabolism
MH  - Transcription Factors/genetics
PMC - PMC3443231
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/10/02 06:00
MHDA- 2013/02/16 06:00
PMCR- 2012/09/14
CRDT- 2012/10/02 06:00
PHST- 2012/07/02 00:00 [received]
PHST- 2012/08/11 00:00 [accepted]
PHST- 2012/10/02 06:00 [entrez]
PHST- 2012/10/02 06:00 [pubmed]
PHST- 2013/02/16 06:00 [medline]
PHST- 2012/09/14 00:00 [pmc-release]
AID - PONE-D-12-20263 [pii]
AID - 10.1371/journal.pone.0045045 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(9):e45045. doi: 10.1371/journal.pone.0045045. Epub 2012 Sep 14.