Document Detail


NHERF-1: modulator of glioblastoma cell migration and invasion.
MedLine Citation:
PMID:  19308292     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The invasive nature of malignant gliomas is a clinical problem rendering tumors incurable by conventional treatment modalities such as surgery, ionizing radiation, and temozolomide. Na(+)/H(+) exchanger regulatory factor 1 (NHERF-1) is a multifunctional adaptor protein, recruiting cytoplasmic signaling proteins and membrane receptors/transporters into functional complexes. This study revealed that NHERF-1 expression is increased in highly invasive cells that reside in the rim of glioblastoma multiforme (GBM) tumors and that NHERF-1 sustains glioma migration and invasion. Gene expression profiles were evaluated from laser capture-microdissected human GBM cells isolated from patient tumor cores and corresponding invaded white matter regions. The role of NHERF-1 in the migration and dispersion of GBM cell lines was examined by reducing its expression with small-interfering RNA followed by radial migration, three-dimensional collagen dispersion, immunofluorescence, and survival assays. The in situ expression of NHERF-1 protein was restricted to glioma cells and the vascular endothelium, with minimal to no detection in adjacent normal brain tissue. Depletion of NHERF-1 arrested migration and dispersion of glioma cell lines and caused an increase in cell-cell cohesiveness. Glioblastoma multiforme cells with depleted NHERF-1 evidenced a marked decrease in stress fibers, a larger cell size, and a more rounded shape with fewer cellular processes. When NHERF-1 expression was reduced, glioma cells became sensitized to temozolomide treatment resulting in increased apoptosis. Taken together, these results provide the first evidence for NHERF-1 as a participant in the highly invasive phenotype of malignant gliomas and implicate NHERF-1 as a possible therapeutic target for treatment of GBM.
Authors:
Kerri L Kislin; Wendy S McDonough; Jennifer M Eschbacher; Brock A Armstrong; Michael E Berens
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neoplasia (New York, N.Y.)     Volume:  11     ISSN:  1476-5586     ISO Abbreviation:  Neoplasia     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-03-24     Completed Date:  2009-05-12     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  100886622     Medline TA:  Neoplasia     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  377-87     Citation Subset:  IM    
Affiliation:
Cancer and Cell Biology Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA.
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MeSH Terms
Descriptor/Qualifier:
Blotting, Western
Brain Neoplasms / genetics,  metabolism*
Cell Adhesion / genetics
Cell Movement / genetics
Fluorescent Antibody Technique
Gene Expression Profiling
Glioblastoma / genetics,  metabolism*
Humans
Image Processing, Computer-Assisted
Immunohistochemistry
Lasers
Microdissection
Neoplasm Invasiveness / genetics*
Oligonucleotide Array Sequence Analysis
Phosphoproteins / genetics,  metabolism*
RNA, Small Interfering
Reverse Transcriptase Polymerase Chain Reaction
Sodium-Hydrogen Antiporter / genetics,  metabolism*
Tissue Array Analysis
Transfection
Grant Support
ID/Acronym/Agency:
5R01NS042262/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Phosphoproteins; 0/RNA, Small Interfering; 0/Sodium-Hydrogen Antiporter; 0/sodium-hydrogen exchanger regulatory factor
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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