Nf2/Merlin controls spinal cord neural progenitor function in a Rac1/ErbB2-dependent manner.

Abstract

OBJECTIVE:

Individuals with the neurofibromatosis type 2 (NF2) cancer predisposition syndrome develop spinal cord glial tumors (ependymomas) that likely originate from neural progenitor cells. Whereas many spinal ependymomas exhibit indolent behavior, the only treatment option for clinically symptomatic tumors is surgery. In this regard, medical therapies are unfortunately lacking due to an incomplete understanding of the critical growth control pathways that govern the function of spinal cord (SC) neural progenitor cells (NPCs).

METHODS:

To identify potential therapeutic targets for these tumors, we leveraged primary mouse Nf2-deficient spinal cord neural progenitor cells.

RESULTS:

We demonstrate that the Nf2 protein, merlin, negatively regulates spinal neural progenitor cell survival and glial differentiation in an ErbB2-dependent manner, and that NF2-associated spinal ependymomas exhibit increased ErbB2 activation. Moreover, we show that Nf2-deficient SC NPC ErbB2 activation results from Rac1-mediated ErbB2 retention at the plasma membrane.

SIGNIFICANCE:

Collectively, these findings establish ErbB2 as a potential rational therapeutic target for NF2-associated spinal ependymoma.

• Authors: Cynthia Garcia, David H Gutmann
• Journal: PloS one (PLoS One) Vol. 9 Issue 5 Pg. e97320 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24817309 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Neurofibromin 2
• Neuropeptides
• Rac1 protein, mouse
• Erbb2 protein, mouse
• Receptor, ErbB-2
• rac1 GTP-Binding Protein

Topics

• Animals
• Blotting, Western
• Cell Differentiation (physiology)
• Cell Fractionation
• Cell Membrane (metabolism)
• Ependymoma (drug therapy, physiopathology)
• Gene Expression Regulation, Neoplastic (physiology)
• Immunohistochemistry
• Mice
• Mice, Knockout
• Neural Stem Cells (metabolism, physiology)
• Neurofibromin 2 (genetics, metabolism)
• Neuropeptides (metabolism)
• Receptor, ErbB-2 (metabolism)
• Spinal Cord Neoplasms (drug therapy, physiopathology)
• rac1 GTP-Binding Protein (metabolism)