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PMID: 18505913 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

Signal transducer and activator of transcription-3: a molecular hub for signaling pathways in gliomas.

Molecular cancer research : MCR ·Vol. 6 ·No. 5 ·2008-05-00 ·Pages 675-84

Brantley EC, Benveniste EN

Abstract

Glioblastoma is the most common and severe primary brain tumor in adults. Its aggressive and infiltrative nature renders the current therapeutics of surgical resection, radiation, and chemotherapy relatively ineffective. Accordingly, recent research has focused on the elucidation of various signal transduction pathways in glioblastoma, particularly aberrant activation. This review focuses on the signal transducer and activator of transcription-3 (STAT-3) signal transduction pathway in the context of this devastating tumor. STAT-3 is aberrantly activated in human glioblastoma tissues, and this activation is implicated in controlling critical cellular events thought to be involved in gliomagenesis, such as cell cycle progression, apoptosis, angiogenesis, and immune evasion. There are no reports of gain-of-function mutations in glioblastoma; rather, the activation of STAT-3 is thought to be a consequence of either dysregulation of upstream kinases or loss of endogenous inhibitors. This review provides detailed insight into the multiple mechanisms of STAT-3 activation in glioblastoma, as well as describing endogenous and chemical inhibitors of this pathway and their clinical significance. In glioblastoma, STAT-3 acts a molecular hub to link extracellular signals to transcriptional control of proliferation, cell cycle progression, and immune evasion. Because STAT-3 plays this central role in glioblastoma signal transduction, it has significant potential as a therapeutic target.

MeSH Terms
Brain Neoplasms/metabolism,pathology Cell Cycle Cell Proliferation Cytokines/metabolism ErbB Receptors/metabolism Gene Expression Regulation, Neoplastic Glioma/metabolism,pathology Humans Immune System Interleukin-6/metabolism Models, Biological STAT3 Transcription Factor/metabolism,physiology Signal Transduction Transcriptional Activation
Chemicals
Cytokines Interleukin-6 STAT3 Transcription Factor STAT3 protein, human ErbB Receptors
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Brantley Emily C
Department of Cell Biology, 1918 University Boulevard, MCLM 395A, University of Alabama at Birmingham, Birmingham, AL 35294-0005, USA.
Benveniste Etty N
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Article Info
Journal
Molecular cancer research : MCR
Abbr.
Mol Cancer Res
ISSN
1541-7786
DOI
10.1158/1541-7786.MCR-07-2180
Published
2008-05-00
Pages
675-84
Language
English
Region
United States
NLM ID
101150042
PMCID
PMC3886801
Subset
IM
Grants
NINDS NIH HHS · R01 NS050665 · United States
NINDS NIH HHS · R21 NS054158 · United States
NCI NIH HHS · P50 CA097247 · United States
NINDS NIH HHS · R01 NS-54158 · United States
NCI NIH HHS · P50 CA-97247 · United States
NINDS NIH HHS · R01 NS050665-03 · United States
External Links
PubMed source DOI: 10.1158/1541-7786.MCR-07-2180 PMC Full Text View journal details
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