Increased Fibroblast Growth Factor-Inducible 14 Expression Levels Promote Glioma Cell Invasion via Rac1 and Nuclear Factor-κB and Correlate with Poor Patient Outcome

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

doi:10.1158/0008-5472.can-06-0418

Cited by 178 publications

(318 citation statements)

References 36 publications

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“…4B). A few studies have indicated that Rho GTPases, especially Rac1 and Cdc42, interact with TWEAK receptor (31,32). However, we found that overexpression of a Rho GDP dissociation inhibitor protein that blocks the activation of RhoA, Rac1, and Cdc42 GTPases (33) did not affect either the activation of MMP-9 promoter or NF-B in myotubes (Fig.…”

Section: Tweak Increases Mmp-9 Production In C2c12 Myotubes and In Skmentioning

confidence: 68%

Tumor Necrosis Factor-related Weak Inducer of Apoptosis Augments Matrix Metalloproteinase 9 (MMP-9) Production in Skeletal Muscle through the Activation of Nuclear Factor-κB-inducing Kinase and p38 Mitogen-activated Protein Kinase

Mittal

Paul

et al. 2009

Journal of Biological Chemistry

108

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Destruction of skeletal muscle extracellular matrix is an important pathological consequence of many diseases involving muscle wasting. However, the underlying mechanisms leading to extracellular matrix breakdown in skeletal muscle tissues remain unknown. Using a microarray approach, we investigated the effect of tumor necrosis factor-related weak inducer of apoptosis (TWEAK), a recently identified muscle-wasting cytokine, on the expression of extracellular proteases in skeletal muscle. Among several other matrix metalloproteinases (MMPs), we found that the expression of MMP-9, a type IV collagenase, was drastically increased in myotubes in response to TWEAK. The level of MMP-9 was also higher in myofibers of TWEAK transgenic mice. TWEAK increased the activation of both classical and alternative nuclear factor-B (NF-B) signaling pathways. Inhibition of NF-B activity blocked the TWEAK-induced production of MMP-9 in myotubes. TWEAK also increased the activation of AP-1, and its inhibition attenuated the TWEAK-induced MMP-9 production. Overexpression of a kinase-dead mutant of NF-B-inducing kinase or IB kinase-␤ but not IB kinase-␣ significantly inhibited the TWEAK-induced activation of MMP-9 promoter. The activation of MMP-9 also involved upstream recruitment of TRAF2 and cIAP2 proteins. TWEAK increased the activity of ERK1/2, JNK1, and p38 MAPK. However, the inhibition of only p38 MAPK blocked the TWEAK-induced expression of MMP-9 in myotubes. Furthermore the loss of body and skeletal muscle weights, inflammation, fiber necrosis, and degradation of basement membrane around muscle fibers were significantly attenuated in Mmp9 knock-out mice on chronic administration of TWEAK protein.The study unveils a novel mechanism of skeletal muscle tissue destruction in pathological conditions.

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Section: Tweak Increases Mmp-9 Production In C2c12 Myotubes and In Skmentioning

confidence: 68%

Tumor Necrosis Factor-related Weak Inducer of Apoptosis Augments Matrix Metalloproteinase 9 (MMP-9) Production in Skeletal Muscle through the Activation of Nuclear Factor-κB-inducing Kinase and p38 Mitogen-activated Protein Kinase

Mittal

Paul

et al. 2009

Journal of Biological Chemistry

108

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“…For example, whereas both soluble TWEAK and memTWEAK are strong stimuli of the alternative NF-kB pathway, only memTWEAK also efficiently triggers the classical NF-kB pathway (24). Several members of the TNFR-associated factor (TRAF) family and Rac1 have been identified as Fn14-interacting molecules, but their relevance for defined aspects of Fn14 signal transduction is poorly understood (25)(26)(27). In molecular terms the best elucidated Fn14 signaling event is presumably TRAF2 recruitment and its relevance for alternative NFkB signaling (28).…”

mentioning

confidence: 99%

TWEAK Inhibits TRAF2-Mediated CD40 Signaling by Destabilization of CD40 Signaling Complexes

Salzmann

Lang

Rosenthal

et al. 2013

The Journal of Immunology

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We found recently that TNF-like weak inducer of apoptosis (TWEAK) and fibroblast growth factor–inducible-14 (Fn14) by virtue of their strong capability to reduce the freely available cytoplasmic pool of TNFR-associated factor (TRAF)2 and cellular inhibitors of apoptosis (cIAPs) antagonize the functions of these molecules in TNFR1 signaling, resulting in sensitization for apoptosis and inhibition of classical NF-κB signaling. In this study, we demonstrate that priming of cells with TWEAK also interferes with activation of the classical NF-κB pathway by CD40. Likewise, there was strong inhibition of CD40 ligand (CD40L)–induced activation of MAPKs in TWEAK-primed cells. FACS analysis and CD40L binding studies revealed unchanged CD40 expression and normal CD40L–CD40 interaction in TWEAK-primed cells. CD40L immunoprecipitates, however, showed severely reduced amounts of CD40 and CD40-associated proteins, indicating impaired formation or reduced stability of CD40L–CD40 signaling complexes. The previously described inhibitory effect of TWEAK on TNFR1 signaling has been traced back to reduced activity of the TNFR1-associated TRAF2–cIAP1/2 ubiquitinase complex and did not affect the stability of the immunoprecipitable TNFR1 receptor complex. Thus, the inhibitory effect of TWEAK on CD40 signaling must be based at least partly on other mechanisms. In line with this, signaling by the CD40-related TRAF2-interacting receptor TNFR2 was also attenuated but still immunoprecipitable in TWEAK-primed cells. Collectively, we show that Fn14 activation by soluble TWEAK impairs CD40L–CD40 signaling complex formation and inhibits CD40 signaling and thus identify the Fn14-TWEAK system as a potential novel regulator of CD40-related cellular functions.

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“…[19][20][21][22] NFκB is constitutively active in many cancers, including gliomas, [23][24][25] and aberrant regulation of NFκB signaling is involved in apoptosis evasion and tumor promotion. 26 In GBM, elevated NFκB signaling is associated with enhanced chemo-and radiation resistance in the mesenchymal subtype. 27 NFκB plays a fundamental role in inhibiting apoptosis by inducing anti-apoptotic factors, such as TRAF1 and cellular inhibitors of apoptosis proteins 1 and 2 (cIAP1/2).…”

Section: Lee Et Al Nfia-nfκb Feed-forward Loop In Gbmmentioning

confidence: 99%

A novel NFIA-NFκB feed-forward loop contributes to glioblastoma cell survival

Lee

Hoxha

Song

2016

NEUONC

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Increased Fibroblast Growth Factor-Inducible 14 Expression Levels Promote Glioma Cell Invasion via Rac1 and Nuclear Factor-κB and Correlate with Poor Patient Outcome

Cited by 178 publications

References 36 publications

Tumor Necrosis Factor-related Weak Inducer of Apoptosis Augments Matrix Metalloproteinase 9 (MMP-9) Production in Skeletal Muscle through the Activation of Nuclear Factor-κB-inducing Kinase and p38 Mitogen-activated Protein Kinase

Tumor Necrosis Factor-related Weak Inducer of Apoptosis Augments Matrix Metalloproteinase 9 (MMP-9) Production in Skeletal Muscle through the Activation of Nuclear Factor-κB-inducing Kinase and p38 Mitogen-activated Protein Kinase

TWEAK Inhibits TRAF2-Mediated CD40 Signaling by Destabilization of CD40 Signaling Complexes

A novel NFIA-NFκB feed-forward loop contributes to glioblastoma cell survival

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