期刊
CURRENT MOLECULAR MEDICINE
卷 13, 期 8, 页码 1241-1249出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1566524011313080002
关键词
Astrocytes; brain tumor stem cells; EGFRvIII; glioblastoma; invasiveness; iNOS; NO; proliferation; STAT3; signaling
资金
- NIH grant [NS064007]
- Canadian Institute of Health Research
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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