Critical role of zinc finger protein 521 in the control of growth, clonogenicity and tumorigenic potential of medulloblastoma cells

Raffaella Spina, Gessica Filocamo, Enrico Iaccino, Stefania Scicchitano, Michela Lupia, Emanuela Chiarella, Tiziana Mega, Francesca Bernaudo, Daniela Pelaggi, Maria Mesuraca, Simonetta Pazzaglia, Samantha Semenkow, Eli E. Bar, Marcel Kool, Stefan Pfister, Heather M. Bond, Charles G Eberhart, Christian Steinkühler, Giovanni Morrone

Research output: Contribution to journalArticle

Abstract

The stem cell-associated transcription co-factor ZNF521 has been implicated in the control of hematopoietic, osteo-adipogenic and neural progenitor cells. ZNF521 is highly expressed in cerebellum and in particular in the neonatal external granule layer that contains candidate medulloblastoma cells-of-origin, and in the majority of human medulloblastomas. Here we have explored its involvement in the control of human and murine medulloblastoma cells. The effect of ZNF521 on growth and tumorigenic potential of human medulloblastoma cell lines as well as primary Ptc1-/+ mouse medulloblastoma cells was investigated in a variety of in vitro and in vivo assays, by modulating its expression using lentiviral vectors carrying the ZNF521 cDNA, or shRNAs that silence its expression. Enforced overexpression of ZNF521 in DAOY medulloblastoma cells significantly increased their proliferation, growth as spheroids and ability to generate clones in single-cell cultures and semisolid media, and enhanced their migratory ability in wound-healing assays. Importantly, ZNF521-expressing cells displayed a greatly enhanced tumorigenic potential in nude mice. All these activities required the ZNF521 N-terminal motif that recruits the nucleosome remodeling and histone deacetylase complex, which might therefore represent an appealing therapeutic target. Conversely, silencing of ZNF521 in human UW228 medulloblastoma cells that display high baseline expression decreased their proliferation, clonogenicity, sphere formation and woundhealing ability. Similarly, Zfp521 silencing in mouse Ptc1-/+ medulloblastoma cells drastically reduced their growth and tumorigenic potential. Our data strongly support the notion that ZNF521, through the recruitment of the NuRD complex, contributes to the clonogenic growth, migration and tumorigenicity of medulloblastoma cells.

Original languageEnglish (US)
Pages (from-to)1280-1292
Number of pages13
JournalOncotarget
Volume4
Issue number8
StatePublished - 2013

Fingerprint

Medulloblastoma
Zinc Fingers
Growth
Proteins
Mi-2 Nucleosome Remodeling and Deacetylase Complex
Stem Cells
Histone Deacetylases
Nude Mice
Wound Healing
Cerebellum
Culture Media
Transcription Factors
Complementary DNA
Clone Cells
Cell Culture Techniques
Cell Line

Keywords

  • Cancer stem cells
  • Cell growth
  • Gene expression
  • Medulloblastoma
  • Tumorigenicity
  • ZNF521

ASJC Scopus subject areas

  • Oncology

Cite this

Spina, R., Filocamo, G., Iaccino, E., Scicchitano, S., Lupia, M., Chiarella, E., ... Morrone, G. (2013). Critical role of zinc finger protein 521 in the control of growth, clonogenicity and tumorigenic potential of medulloblastoma cells. Oncotarget, 4(8), 1280-1292.

Critical role of zinc finger protein 521 in the control of growth, clonogenicity and tumorigenic potential of medulloblastoma cells. / Spina, Raffaella; Filocamo, Gessica; Iaccino, Enrico; Scicchitano, Stefania; Lupia, Michela; Chiarella, Emanuela; Mega, Tiziana; Bernaudo, Francesca; Pelaggi, Daniela; Mesuraca, Maria; Pazzaglia, Simonetta; Semenkow, Samantha; Bar, Eli E.; Kool, Marcel; Pfister, Stefan; Bond, Heather M.; Eberhart, Charles G; Steinkühler, Christian; Morrone, Giovanni.

In: Oncotarget, Vol. 4, No. 8, 2013, p. 1280-1292.

Research output: Contribution to journalArticle

Spina, R, Filocamo, G, Iaccino, E, Scicchitano, S, Lupia, M, Chiarella, E, Mega, T, Bernaudo, F, Pelaggi, D, Mesuraca, M, Pazzaglia, S, Semenkow, S, Bar, EE, Kool, M, Pfister, S, Bond, HM, Eberhart, CG, Steinkühler, C & Morrone, G 2013, 'Critical role of zinc finger protein 521 in the control of growth, clonogenicity and tumorigenic potential of medulloblastoma cells', Oncotarget, vol. 4, no. 8, pp. 1280-1292.
Spina R, Filocamo G, Iaccino E, Scicchitano S, Lupia M, Chiarella E et al. Critical role of zinc finger protein 521 in the control of growth, clonogenicity and tumorigenic potential of medulloblastoma cells. Oncotarget. 2013;4(8):1280-1292.
Spina, Raffaella ; Filocamo, Gessica ; Iaccino, Enrico ; Scicchitano, Stefania ; Lupia, Michela ; Chiarella, Emanuela ; Mega, Tiziana ; Bernaudo, Francesca ; Pelaggi, Daniela ; Mesuraca, Maria ; Pazzaglia, Simonetta ; Semenkow, Samantha ; Bar, Eli E. ; Kool, Marcel ; Pfister, Stefan ; Bond, Heather M. ; Eberhart, Charles G ; Steinkühler, Christian ; Morrone, Giovanni. / Critical role of zinc finger protein 521 in the control of growth, clonogenicity and tumorigenic potential of medulloblastoma cells. In: Oncotarget. 2013 ; Vol. 4, No. 8. pp. 1280-1292.
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