title: Ferritin heavy chain is a negative regulator of ovarian cancer stem cell expansion and epithelial to mesenchymal transition.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  In this paper we uncover a new function of FHC in the control of cancer stem cells.
authors: Centro di Ricerca di Biochimica e Biologia Molecolare Avanzata, Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi "Magna Graecia", Catanzaro, Italy.
authors: Nadia
authors: N
authors: Lobello
authors: Centro di Ricerca di Biochimica e Biologia Molecolare Avanzata, Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi "Magna Graecia", Catanzaro, Italy.
authors: Flavia
authors: F
authors: Biamonte
authors: Dipartimento di Medicina Clinica e Molecolare, Sapienza Università di Roma, Italy.|Laboratorio di Biologia Cellulare e Molecolare, Dipartimento di Chirurgia "P. Valdoni", Sapienza Università di Roma, Italy.
authors: Maria Elena
authors: ME
authors: Pisanu
authors: Centro di Ricerca di Biochimica e Biologia Molecolare Avanzata, Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi "Magna Graecia", Catanzaro, Italy.
authors: Maria Concetta
authors: MC
authors: Faniello
authors: Faculty of Pharmacy, University of Ljubljana, Slovenia.
authors: Žiga
authors: Ž
authors: Jakopin
authors: Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi "Magna Graecia", Catanzaro, Italy.
authors: Emanuela
authors: E
authors: Chiarella
authors: Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi "Magna Graecia", Catanzaro, Italy.|Centro Interdipartimentale di Servizi e Ricerca, Università degli Studi "Magna Graecia", Catanzaro, Italy.
authors: Emilia Dora
authors: ED
authors: Giovannone
authors: Dipartimento di Medicina Clinica e Molecolare, Sapienza Università di Roma, Italy.|Laboratorio di Biologia Cellulare e Molecolare, Dipartimento di Chirurgia "P. Valdoni", Sapienza Università di Roma, Italy.
authors: Rita
authors: R
authors: Mancini
authors: Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione G. Pascale", Napoli, Italy.
authors: Gennaro
authors: G
authors: Ciliberto
authors: Centro di Ricerca di Biochimica e Biologia Molecolare Avanzata, Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi "Magna Graecia", Catanzaro, Italy.
authors: Giovanni
authors: G
authors: Cuda
authors: Centro di Ricerca di Biochimica e Biologia Molecolare Avanzata, Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi "Magna Graecia", Catanzaro, Italy.
authors: Francesco
authors: F
authors: Costanzo
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000080924:Aldehyde Dehydrogenase 1 Family; D001052:Apoferritins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D050356:Lipid Metabolism; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000378:metabolism; D000071317:Nanog Homeobox Protein / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D011379:Prognosis; D050697:Retinal Dehydrogenase; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: D035683:MicroRNAs; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D014746:Vimentin; D001052:Apoferritins; C523776:SCD1 protein, human; D013230:Stearoyl-CoA Desaturase; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase
keywords: EMT; cancer stem cells; ferritin heavy chain; miRNAs; ovarian cancer