Functional characterization of full-length BARD1 strengthens its role as a tumor suppressor in neuroblastoma

Flora Cimmino, Marianna Avitabile, Vito Alessandro Lasorsa, Lucia Pezone, Antonella Cardinale, Annalaura Montella, Sueva Cantalupo, Achille Iolascon, Mario Capasso

Research output: Contribution to journalArticle

Abstract

BARD1 is associated with the development of high-risk neuroblastoma patients. Particularly, the expression of full length (FL) isoform, FL BARD1, correlates to high-risk neuroblastoma development and its inhibition is sufficient to induce neuroblastoma cells towards a worst phenotype. Here we have investigated the mechanisms of FL BARD1 in neuroblastoma cell lines depleted for FL BARD1 expression. We have shown that FL BARD1 expression protects the cells from spontaneous DNA damage and from damage accumulated after irradiation. We demonstrated a role for FL BARD1 as tumor suppressor to prevent unscheduled mitotic entry of DNA damaged cells and to lead to death cells that have bypassed cell cycle checkpoints. FL BARD1-depleted cells that have survived to checkpoints acquire features of aggressiveness. Overall, our results show that FL BARD1 may defend cells against cancer and prevent malignant transformation of cells.

Original languageEnglish
Pages (from-to)1495-1504
Number of pages10
JournalJournal of Cancer
Volume11
Issue number6
DOIs
Publication statusPublished - Jan 1 2020

Keywords

  • BARD1
  • Neuroblastoma
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Cimmino, F., Avitabile, M., Lasorsa, V. A., Pezone, L., Cardinale, A., Montella, A., Cantalupo, S., Iolascon, A., & Capasso, M. (2020). Functional characterization of full-length BARD1 strengthens its role as a tumor suppressor in neuroblastoma. Journal of Cancer, 11(6), 1495-1504. https://doi.org/10.7150/jca.36164