title: Down-regulation of the Lamin A/C in neuroblastoma triggers the expansion of tumor initiating cells.
abstract: Tumor-initiating cells constitute a population within a tumor mass that shares properties with normal stem cells and is considered responsible for therapy failure in many cancers. We have previously demonstrated that knockdown of the nuclear envelope component Lamin A/C in human neuroblastoma cells inhibits retinoic acid-mediated differentiation and results in a more aggressive phenotype. In addition, Lamin A/C is often lost in advanced tumors and changes in the nuclear envelope composition occur during tumor progression. Based on our previous data and considering that Lamin A/C is expressed in differentiated tissues, we hypothesize that the lack of Lamin A/C could predispose cells toward a stem-like phenotype, thus influencing the development of tumor-initiating cells in neuroblastoma. This paper demonstrates that knockdown of Lamin A/C triggers the development of a tumor-initiating cell population with self-renewing features in human neuroblastoma cells. We also demonstrates that the development of TICs is due to an increased expression of MYCN gene and that in neuroblastoma exists an inverse relationship between LMNA and MYCN expression.
authors.affiliation: Institute of Cell Biology and Neurobiology-CNR, Monterotondo, Rome, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Nardella
authors.affiliation: Institute of Cell Biology and Neurobiology-CNR, Monterotondo, Rome, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Guglielmi
authors.affiliation: Institute of Cell Biology and Neurobiology-CNR, Monterotondo, Rome, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Musa
authors.affiliation: Institute of Cell Biology and Neurobiology-CNR, Monterotondo, Rome, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Iannetti
authors.affiliation: Institute of Cell Biology and Neurobiology-CNR, Monterotondo, Rome, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Maresca
authors.affiliation: S.Pietro Hospital Fatebenefratelli, Rome, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Amendola
authors.affiliation: Regina Elena Cancer Institute, Rome, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Porru
authors.affiliation: UOD Cytopathology, Department of Molecular and Clinical Medicine, Faculty of Medicine and Psychology, Sapienza University, Rome, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Carico
authors.affiliation: Department of Experimental Oncology, National Cancer Institute-IRCCS "Fondazione G. Pascale", Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sessa
authors.affiliation: Department of Experimental Oncology, National Cancer Institute-IRCCS "Fondazione G. Pascale", Naples, Italy.
authors.forename: Rosalba
authors.initials: R
authors.lastname: Camerlingo
authors.affiliation: Department of Paediatrics and Infantile Neuropsychiatry, Sapienza University, Rome, Italy.|School of Reproductive and Developmental Medicine, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Carlo
authors.initials: C
authors.lastname: Dominici
authors.affiliation: Department of Paediatrics and Infantile Neuropsychiatry, Sapienza University, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Megiorni
authors.affiliation: Institute of Cell Biology and Neurobiology-CNR, Monterotondo, Rome, Italy.
authors.forename: Marika
authors.initials: M
authors.lastname: Milan
authors.affiliation: Institute of Cell Biology and Neurobiology-CNR, Monterotondo, Rome, Italy.|I.R.C.C.S Multimedica, Scientific and Technology Pole, Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bearzi
authors.affiliation: Institute of Cell Biology and Neurobiology-CNR, Monterotondo, Rome, Italy.|I.R.C.C.S Multimedica, Scientific and Technology Pole, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Rizzi
authors.affiliation: Department of Experimental Oncology, National Cancer Institute-IRCCS "Fondazione G. Pascale", Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pirozzi
authors.affiliation: Regina Elena Cancer Institute, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Leonetti
authors.affiliation: S.Pietro Hospital Fatebenefratelli, Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bucci
authors.affiliation: Institute of Cell Biology and Neurobiology-CNR, Monterotondo, Rome, Italy.
authors.forename: Delio
authors.initials: D
authors.lastname: Mercanti
authors.affiliation: Institute of Cell Biology and Neurobiology-CNR, Monterotondo, Rome, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Felsani
authors.affiliation: Institute of Cell Biology and Neurobiology-CNR, Monterotondo, Rome, Italy.
authors.forename: Igea
authors.initials: I
authors.lastname: D'Agnano
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000066673:Cell Self Renewal; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006801:Humans; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008819:Mice, Nude; D000071447:N-Myc Proto-Oncogene Protein; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D034622:RNA Interference; D015398:Signal Transduction; D018874:Spheroids, Cellular; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins
keywords: Lamin A/C; MYCN; TICs; miRNAs; neuroblastoma