Faculty Collaboration Database

NOTCH3 is a prognostic factor that promotes glioma cell proliferation, migration and invasion via activation of CCND1 and EGFR. PLoS One 2013;8(10):e77299

Date

10/22/2013

Pubmed ID

24143218

Pubmed Central ID

PMC3797092

DOI

10.1371/journal.pone.0077299

Scopus ID

2-s2.0-84885453485 (requires institutional sign-in at Scopus site)   44 Citations

Abstract

Using a GWA analysis of a comprehensive glioma specimen population, we identified whole gain of chromosome 19 as one of the major chromosomal aberrations that correlates to patients' outcomes. Our analysis of significant loci revealed for the first time NOTCH3 as one of the most significant amplification. NOTCH3 amplification is associated with worse outcome compared to tumors with non-amplified locus. NOTCH receptors (NOTCH1-4) are key positive regulators of cell-cell interactions, angiogenesis, cell adhesion and stem cell niche development which have been shown to play critical roles in several human cancers. Our objective is to determine the molecular roles of NOTCH3 in glioma pathogenesis and aggressiveness. Here we show for the first time that NOTCH3 plays a major role in glioma cell proliferation, cell migration, invasion and apoptosis. Therefore, our study uncovers the prognostic value and the oncogenic function of NOTCH3 in gliomagenesis and supports NOTCH3 as a promising target of therapy in high grade glioma. Our studies allowed the identification of a subset of population that may benefit from GSI- or anti-NOTCH3- based therapies. This may lead to the design of novel strategies to improve therapeutic outcome of patients with glioma by establishing medical and scientific basis for personalized chemotherapies.

Author List

Alqudah MA, Agarwal S, Al-Keilani MS, Sibenaller ZA, Ryken TC, Assem M

Author

Mahfoud Assem PharmD Associate Professor in the School of Pharmacy Administration department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Apoptosis
Cell Cycle
Cell Line, Tumor
Cell Movement
Cell Proliferation
Cyclin D1
ErbB Receptors
Gene Knockdown Techniques
Glioma
Humans
Neoplasm Grading
Neoplasm Invasiveness
Oncogenes
Prognosis
Receptor, Notch3
Receptors, Notch