Ferritin heavy chain is a negative regulator of ovarian cancer stem cell expansion and epithelial to mesenchymal transition

Nadia Lobello, Flavia Biamonte, Maria Elena Pisanu, Maria Concetta Faniello, Žiga Jakopin, Emanuela Chiarella, Emilia Dora Giovannone, Rita Mancini, Gennaro Ciliberto, Giovanni Cuda, Francesco Costanzo

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)62019-62033
Number of pages15
JournalOncotarget
Volume7
Issue number38
DOIs
Publication statusPublished - 2016

Fingerprint

Apoferritins
Epithelial-Mesenchymal Transition
Neoplastic Stem Cells
Ovarian Neoplasms
MicroRNAs
Vimentin
Microarray Analysis
Ferritins
Lipid Metabolism
Oxidation-Reduction
Neoplasms
Cell Survival
Stem Cells
Iron
Databases
Polymerase Chain Reaction

Keywords

  • Cancer stem cells
  • EMT
  • Ferritin heavy chain
  • MiRNAs
  • Ovarian cancer

ASJC Scopus subject areas

  • Oncology

Cite this

Lobello, N., Biamonte, F., Pisanu, M. E., Faniello, M. C., Jakopin, Ž., Chiarella, E., ... Costanzo, F. (2016). Ferritin heavy chain is a negative regulator of ovarian cancer stem cell expansion and epithelial to mesenchymal transition. Oncotarget, 7(38), 62019-62033. https://doi.org/10.18632/oncotarget.11495

Ferritin heavy chain is a negative regulator of ovarian cancer stem cell expansion and epithelial to mesenchymal transition. / Lobello, Nadia; Biamonte, Flavia; Pisanu, Maria Elena; Faniello, Maria Concetta; Jakopin, Žiga; Chiarella, Emanuela; Giovannone, Emilia Dora; Mancini, Rita; Ciliberto, Gennaro; Cuda, Giovanni; Costanzo, Francesco.

In: Oncotarget, Vol. 7, No. 38, 2016, p. 62019-62033.

Research output: Contribution to journalArticle

Lobello, N, Biamonte, F, Pisanu, ME, Faniello, MC, Jakopin, Ž, Chiarella, E, Giovannone, ED, Mancini, R, Ciliberto, G, Cuda, G & Costanzo, F 2016, 'Ferritin heavy chain is a negative regulator of ovarian cancer stem cell expansion and epithelial to mesenchymal transition', Oncotarget, vol. 7, no. 38, pp. 62019-62033. https://doi.org/10.18632/oncotarget.11495
Lobello, Nadia ; Biamonte, Flavia ; Pisanu, Maria Elena ; Faniello, Maria Concetta ; Jakopin, Žiga ; Chiarella, Emanuela ; Giovannone, Emilia Dora ; Mancini, Rita ; Ciliberto, Gennaro ; Cuda, Giovanni ; Costanzo, Francesco. / Ferritin heavy chain is a negative regulator of ovarian cancer stem cell expansion and epithelial to mesenchymal transition. In: Oncotarget. 2016 ; Vol. 7, No. 38. pp. 62019-62033.
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