Abstract
Glioblastoma is the most aggressive adult primary brain tumor. Although progress has been made in understanding the molecular mechanisms underlying these tumors, current treatments are ineffective. Recent studies have identified iNOS as a critical regulator of glial transformation downstream of EGFRvIII/STAT3 signaling, a key oncogenic pathway in glioblastoma. STAT3 directly binds the promoter of the iNOS gene and thereby stimulates its expression. Importantly, inhibition of iNOS by genetic and pharmacological approaches impedes glial cell proliferation, invasiveness, and tumor growth in vivo. iNOS expression is also elevated in a population of human brain tumor stem cells (BTSCs), and iNOS is required for BTSC proliferation and tumorigenesis. Together, these findings suggest that development of iNOS-targeted therapies may prove valuable in the treatment of glioblastoma. Here, we review our current understanding of iNOS signaling in the regulation of glioblastoma pathogenesis and the potential mechanisms by which iNOS inhibition might suppress the malignant behavior of these devastating tumors.
Keywords: Astrocytes, brain tumor stem cells, EGFRvIII, glioblastoma, invasiveness, iNOS, NO, proliferation, STAT3, signaling.
Current Molecular Medicine
Title:iNOS: A Potential Therapeutic Target for Malignant Glioma
Volume: 13 Issue: 8
Author(s): A. Jahani-Asl and A. Bonni
Affiliation:
Keywords: Astrocytes, brain tumor stem cells, EGFRvIII, glioblastoma, invasiveness, iNOS, NO, proliferation, STAT3, signaling.
Abstract: Glioblastoma is the most aggressive adult primary brain tumor. Although progress has been made in understanding the molecular mechanisms underlying these tumors, current treatments are ineffective. Recent studies have identified iNOS as a critical regulator of glial transformation downstream of EGFRvIII/STAT3 signaling, a key oncogenic pathway in glioblastoma. STAT3 directly binds the promoter of the iNOS gene and thereby stimulates its expression. Importantly, inhibition of iNOS by genetic and pharmacological approaches impedes glial cell proliferation, invasiveness, and tumor growth in vivo. iNOS expression is also elevated in a population of human brain tumor stem cells (BTSCs), and iNOS is required for BTSC proliferation and tumorigenesis. Together, these findings suggest that development of iNOS-targeted therapies may prove valuable in the treatment of glioblastoma. Here, we review our current understanding of iNOS signaling in the regulation of glioblastoma pathogenesis and the potential mechanisms by which iNOS inhibition might suppress the malignant behavior of these devastating tumors.
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Cite this article as:
Jahani-Asl A. and Bonni A., iNOS: A Potential Therapeutic Target for Malignant Glioma, Current Molecular Medicine 2013; 13 (8) . https://dx.doi.org/10.2174/1566524011313080002
DOI https://dx.doi.org/10.2174/1566524011313080002 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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