Down-regulation of the Lamin A/C in neuroblastoma triggers the expansion of tumor initiating cells

Marta Nardella, Loredana Guglielmi, Carla Musa, Ilaria Iannetti, Giovanna Maresca, Donatella Amendola, Manuela Porru, Elisabetta Carico, Giuseppe Sessa, Rosalba Camerlingo, Carlo Dominici, Francesca Megiorni, Marika Milan, Claudia Bearzi, Roberto Rizzi, Giuseppe Pirozzi, Carlo Leonetti, Barbara Bucci, Delio Mercanti, Armando FelsaniIgea D'Agnano

Research output: Contribution to journalArticlepeer-review

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 acidmediated 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 tumorinitiating 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.

Original languageEnglish
Pages (from-to)32821-32840
Number of pages20
JournalOncotarget
Volume6
Issue number32
DOIs
Publication statusPublished - 2015

Keywords

  • Lamin A/C
  • MiRNAs
  • MYCN
  • Neuroblastoma
  • TICs

ASJC Scopus subject areas

  • Oncology

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