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Ferritin heavy chain is a negative regulator of ovarian cancer stem cell
expansion and epithelial to mesenchymal transition
#MMPMID27566559
Lobello N
; Biamonte F
; Pisanu ME
; Faniello MC
; Jakopin ?
; Chiarella E
; Giovannone ED
; Mancini R
; Ciliberto G
; Cuda G
; Costanzo F
Oncotarget
2016[Sep]; 7
(38
): 62019-62033
PMID27566559
show ga
OBJECTIVES: Ferritin is the major intracellular iron storage protein essential
for maintaining the cellular redox status. In recent years ferritin heavy chain
(FHC) has been shown to be involved also in the control of cancer cell growth.
Analysis of public microarray databases in ovarian cancer revealed a correlation
between low FHC expression levels and shorter survival. To better understand the
role of FHC in cancer, we have silenced the FHC gene in SKOV3 cells. RESULTS:
FHC-KO significantly enhanced cell viability and induced a more aggressive
behaviour. FHC-silenced cells showed increased ability to form 3D spheroids and
enhanced expression of NANOG, OCT4, ALDH and Vimentin. These features were
accompanied by augmented expression of SCD1, a major lipid metabolism enzyme. FHC
apparently orchestrates part of these changes by regulating a network of miRNAs.
METHODS: FHC-silenced and control shScr SKOV3 cells were monitored for changes in
proliferation, migration, ability to propagate as 3D spheroids and for the
expression of stem cell and epithelial-to-mesenchymal-transition (EMT) markers.
The expression of three miRNAs relevant to spheroid formation or EMT was assessed
by q-PCR. CONCLUSIONS: In this paper we uncover a new function of FHC in the
control of cancer stem cells.
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