Oncotarget

Research Papers:

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 and Francesco Costanzo

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Oncotarget. 2016; 7:62019-62033. https://doi.org/10.18632/oncotarget.11495

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Abstract

Nadia Lobello1,*, Flavia Biamonte1,*, Maria Elena Pisanu2,3, Maria Concetta Faniello1, Žiga Jakopin4, Emanuela Chiarella5, Emilia Dora Giovannone5,6, Rita Mancini2,3, Gennaro Ciliberto7, Giovanni Cuda1,*, Francesco Costanzo1,*

1Centro di Ricerca di Biochimica e Biologia Molecolare Avanzata, Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi “Magna Graecia”, Catanzaro, Italy

2Dipartimento di Medicina Clinica e Molecolare, Sapienza Università di Roma, Italy

3Laboratorio di Biologia Cellulare e Molecolare, Dipartimento di Chirurgia “P. Valdoni”, Sapienza Università di Roma, Italy

4Faculty of Pharmacy, University of Ljubljana, Slovenia

5Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi “Magna Graecia”, Catanzaro, Italy

6Centro Interdipartimentale di Servizi e Ricerca, Università degli Studi “Magna Graecia”, Catanzaro, Italy

7Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione G. Pascale”, Napoli, Italy

*These authors contributed equally to this work

Correspondence to:

Gennaro Ciliberto, email: [email protected]

Keywords: ferritin heavy chain, ovarian cancer, cancer stem cells, EMT, miRNAs

Received: February 28, 2016     Accepted: August 09, 2016     Published: August 22, 2016

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.


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