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2016 ; 16
(1
): 700
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Identification of epigenetic factors regulating the mesenchyme to epithelium
transition by RNA interference screening in breast cancer cells
#MMPMID27581651
Gregoire JM
; Fleury L
; Salazar-Cardozo C
; Alby F
; Masson V
; Arimondo PB
; Ausseil F
BMC Cancer
2016[Aug]; 16
(1
): 700
PMID27581651
show ga
BACKGROUND: In breast cancer, the epithelial to mesenchyme transition (EMT) is
associated to tumour dissemination, drug resistance and high relapse risks. It is
partly controlled by epigenetic modifications such as histone acetylation and
methylation. The identification of genes involved in these reversible
modifications represents an interesting therapeutic strategy to fight metastatic
disease by inducing mesenchymal cell differentiation to an epithelial phenotype.
METHODS: We designed a siRNA library based on chromatin modification-related to
functional domains and screened it in the mesenchymal breast cancer cell line
MDA-MB-231. The mesenchyme to epithelium transition (MET) activation was studied
by following human E-CADHERIN (E-CAD) induction, a specific MET marker, and cell
morphology. Candidate genes were validated by studying the expression of several
differential marker genes and their impact on cell migration. RESULTS: The screen
led to the identification of 70 gene candidates among which some are described to
be, directly or indirectly, involved in EMT like ZEB1, G9a, SMAD5 and SMARCD3. We
also identified the DOT1L as involved in EMT regulation in MDA-MB-231. Moreover,
for the first time, KAT5 gene was linked to the maintenance of the mesenchymal
phenotype. CONCLUSIONS: A multi-parametric RNAi screening approach was developed
to identify new EMT regulators such as KAT5 in the triple negative breast cancer
cell line MDA-MB-231.