Activated EGFR signaling increases proliferation, survival,and migration and blocks neuronal differentiation in post-natal neural stem cells

Angel Ayuso-Sacido, Jennifer A. Moliterno, Sebila Kratovac, Gurpreet S. Kapoor, Donald M. O'Rourke, Eric C. Holland, Jose Manuel Garci'a-Verdugo, Neeta Roy, John A. Boockvar

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Recent evidence supports the notion that transformation of undifferentiated neural stem cell (NSC) precursors may contribute to the development of glioblastoma multiforme (GBM). The over-expression and mutation of the epidermal growth factor receptor (EGFR), along with other cellular pathway mutations, plays a significant role in GBM maintenance progression. Though EGFR signaling is important in determining neural cell fate and conferring astrocyte differentiation, there is a limited understanding of its role in NSC and tumor stem cell (TSC) biology. We hypothesized that EGFR expression and mutation in post-natal NSCs may contribute to cellular aggressiveness including enhanced cellular proliferation, survival and migration. Stable subclones of C17.2 murine NSCs were transfected to over-express either the wild-type EGFR (wtEGFR) or its most common mutated variant EGFRvIII. Activated EGFR signaling in these cells induced behaviors characteristic of GBM TSCs, including enhanced proliferation, survival and migration, even in the absence of EGF ligand. wtEGFR activation was also found to block neuronal differentiation and was associated with a dramatic increase in chemotaxis in the presence of EGF. EGFRvIII expression lead to an increase in NSC proliferation and survival, while it simultaneously blocked neuronal differentiation and promoted glial fate. Our findings suggest that activated EGFR signaling enhances the aggressiveness of NSCs. Understanding the regulatory mechanisms of NSCs may lend insight into deregulated mechanisms of GBM TSC invasion, proliferation, survival and resistance to current treatment modalities.

Original languageEnglish (US)
Pages (from-to)323-337
Number of pages15
JournalJournal of Neuro-Oncology
Volume97
Issue number3
DOIs
StatePublished - May 1 2010
Externally publishedYes

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Neural Stem Cells
Epidermal Growth Factor Receptor
Glioblastoma
Neoplastic Stem Cells
Cell Proliferation
Epidermal Growth Factor
Mutation
Chemotaxis
Neuroglia
Astrocytes
Cell Biology
Cell Survival
Maintenance
Ligands

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cancer Research
  • Oncology
  • Neurology

Cite this

Ayuso-Sacido, A., Moliterno, J. A., Kratovac, S., Kapoor, G. S., O'Rourke, D. M., Holland, E. C., ... Boockvar, J. A. (2010). Activated EGFR signaling increases proliferation, survival,and migration and blocks neuronal differentiation in post-natal neural stem cells. Journal of Neuro-Oncology, 97(3), 323-337. https://doi.org/10.1007/s11060-009-0035-x

Activated EGFR signaling increases proliferation, survival,and migration and blocks neuronal differentiation in post-natal neural stem cells. / Ayuso-Sacido, Angel; Moliterno, Jennifer A.; Kratovac, Sebila; Kapoor, Gurpreet S.; O'Rourke, Donald M.; Holland, Eric C.; Garci'a-Verdugo, Jose Manuel; Roy, Neeta; Boockvar, John A.

In: Journal of Neuro-Oncology, Vol. 97, No. 3, 01.05.2010, p. 323-337.

Research output: Contribution to journalArticle

Ayuso-Sacido, A, Moliterno, JA, Kratovac, S, Kapoor, GS, O'Rourke, DM, Holland, EC, Garci'a-Verdugo, JM, Roy, N & Boockvar, JA 2010, 'Activated EGFR signaling increases proliferation, survival,and migration and blocks neuronal differentiation in post-natal neural stem cells', Journal of Neuro-Oncology, vol. 97, no. 3, pp. 323-337. https://doi.org/10.1007/s11060-009-0035-x
Ayuso-Sacido, Angel ; Moliterno, Jennifer A. ; Kratovac, Sebila ; Kapoor, Gurpreet S. ; O'Rourke, Donald M. ; Holland, Eric C. ; Garci'a-Verdugo, Jose Manuel ; Roy, Neeta ; Boockvar, John A. / Activated EGFR signaling increases proliferation, survival,and migration and blocks neuronal differentiation in post-natal neural stem cells. In: Journal of Neuro-Oncology. 2010 ; Vol. 97, No. 3. pp. 323-337.
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