Increased fibroblast growth factor-inducible 14 expression levels promote glioma cell invasion via Rac1 and nuclear factor-kappaB and correlate with poor patient outcome.

Increased fibroblast growth factor-inducible 14 expression levels promote glioma cell invasion via Rac1 and nuclear factor-kappaB and correlate with poor patient outcome. Research Abstract Details 

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Increased fibroblast growth factor-inducible 14 expression levels promote glioma cell invasion via Rac1 and nuclear factor-kappaB and correlate with poor patient outcome. Abstract Text:

Nhan L Tran,Wendy S McDonough,Benjamin A Savitch,Shannon P Fortin,Jeffrey A Winkles,Marc Symons,Mitsutoshi Nakada,Heather E Cunliffe,Galen Hostetter,Dominique B Hoelzinger,Jessica L Rennert,Jennifer S Michaelson,Linda C Burkly,Christopher A Lipinski,Joseph C Loftus,Luigi Mariani,Michael E Berens,

Glial tumors progress to malignant grades by heightened proliferation and relentless dispersion throughout the central nervous system. Understanding genetic and biochemical processes that foster these behaviors is likely to reveal specific and effective targets for therapeutic intervention. Our current report shows that the fibroblast growth factor-inducible 14 (Fn14), a member of the tumor necrosis factor (TNF) receptor superfamily, is expressed at high levels in migrating glioma cells in vitro and invading glioma cells in vivo. Forced Fn14 overexpression stimulates glioma cell migration and invasion, and depletion of Rac1 by small interfering RNA inhibits this cellular response. Activation of Fn14 signaling by the ligand TNF-like weak inducer of apoptosis (TWEAK) stimulates migration and up-regulates expression of Fn14; this TWEAK effect requires Rac1 and nuclear factor-kappaB (NF-kappaB) activity. The Fn14 promoter region contains NF-kappaB binding sites, which mediate positive feedback causing sustained overexpression of Fn14 and enduring glioma cell invasion. Furthermore, Fn14 gene expression levels increase with glioma grade and inversely correlate with patient survival. These results show that the Fn14 cascade operates as a positive feedback mechanism for elevated and sustained Fn14 expression. Such a feedback loop argues for aggressive targeting of the Fn14 axis as a unique and specific driver of glioma malignant behavior.

Increased fibroblast growth factor-inducible 14 expression levels promote glioma cell invasion via Rac1 and nuclear factor-kappaB and correlate with poor patient outcome. Publishing Authors By Initials

NL Tran,WS McDonough,BA Savitch,SP Fortin,JA Winkles,M Symons,M Nakada,HE Cunliffe,G Hostetter,DB Hoelzinger,JL Rennert,JS Michaelson,LC Burkly,CA Lipinski,JC Loftus,L Mariani,ME Berens,

For similar enzymes and coenzymes: enzymes: hydrolases: acid anhydride hydrolases: gtp phosphohydrolases: gtp-binding proteins: monomeric gtp-binding proteins: rho gtp-binding proteins: rac gtp-binding proteins: rac1 gtp-binding protein research abstracts see: enzymes and coenzymes: enzymes: hydrolases: acid anhydride hydrolases: gtp phosphohydrolases: gtp-binding proteins: monomeric gtp-binding proteins: rho gtp-binding proteins: rac gtp-binding proteins: rac1 gtp-binding protein research

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Increased fibroblast growth factor-inducible 14 expression levels promote glioma cell invasion via Rac1 and nuclear factor-kappaB and correlate with poor patient outcome. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Cancer research

VOLUME: 66

Page Numbers: 9535-42

Journal Abbreviation: Cancer Res.

ISSN: 1538-7445

DAY: 1

MONTH: Oct

YEAR: 2006

Increased fibroblast growth factor-inducible 14 expression levels promote glioma cell invasion via Rac1 and nuclear factor-kappaB and correlate with poor patient outcome. Information

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LANGUAGE: eng

NlmUniqueID: 2984705

Increased fibroblast growth factor-inducible 14 expression levels promote glioma cell invasion via Rac1 and nuclear factor-kappaB and correlate with poor patient outcome. Keywords Mesh Terms:

KEYWORDS: rac1 GTP-Binding Protein

MESH TERMS: physiology

Chemical & Substance for Abstract: Increased fibroblast growth factor-inducible 14 expression levels promote glioma cell invasion via Rac1 and nuclear factor-kappaB and correlate with poor patient outcome. Information

Substance Name: rac1 GTP-Binding Protein

Registry Number: EC 3.6.5.2

Grant and Affiliation Information for Increased fibroblast growth factor-inducible 14 expression levels promote glioma cell invasion via Rac1 and nuclear factor-kappaB and correlate with poor patient outcome.

AFFILIATION: Cancer and Cell Biology Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA.

Country: United States

AGENCY: United States NINDS

GRANT: NS-42262

ACRONYM: NS

MEDLINETA: Cancer Res

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