TWEAK, a member of the TNF superfamily, is a multifunctional cytokine that binds the TweakR/Fn14 receptor

Wiley, Steven R.; Winkles, Jeffrey A.

doi:10.1016/s1359-6101(03)00019-4

Cited by 252 publications

(229 citation statements)

References 42 publications

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“…TNFRSF12A is a precursor of tumor necrosis factor receptor superfamily member FN14, which involves the process of apoptosis, cell adhesion, and cell motility. Elevated FN14 expression was found in human liver cancer cell lines and hepatocellular carcinoma specimens (Meighan-Mantha et al, 1999;Wiley and Winkles, 2003). Both genes, CXCL3 and TNFRSF12A, are involved in cytokinecytokine receptor interaction, a cancer-related pathway.…”

Section: Discussionmentioning

confidence: 97%

Transcriptional profiling suggests that Barrett's metaplasia is an early intermediate stage in esophageal adenocarcinogenesis

Wang

Zhan

Yin³

et al. 2006

Oncogene

112

106

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To investigate the relationship between Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), we determined gene expression profiles of discrete pathological stages of esophageal neoplasia using a sequence-verified human cDNA microarray. Fifty one RNAs, comprising 24 normal esophagi (NE), 18 BEs, and nine EACs were hybridized to cDNA microarrays. Five statistical analyses were used for the data analysis. Genes showing significantly different expression levels among the three sample groups were identified. Genes were grouped into functional categories based on the Gene Ontology Consortium. Surprisingly, the expression pattern of BE was significantly more similar to EAC than to NE, notwithstanding the known histopathologic differences between BE and EAC. The pattern of NE was clearly distinct from that of EAC. Thirty-six genes were the most differentially modulated, according to these microarray data, in BE-associated neoplastic progression. Twelve genes were significantly differentially expressed in cancer-associated BE's plus EAC (as a single combined tissue group) vs noncancer-associated BE's. These genes represent potential biomarkers to diagnose EAC at its early stages. Our results demonstrate that molecular events at the transcriptional level in BE are remarkably similar to BE's-associated adenocarcinoma of the esophagus. This finding alarmingly implies that BE is biologically closer to cancer than to normal esophagus, and that the cancer risk of BE is perhaps higher than we had imagined. These findings suggest that changes modulated at the molecular biologic level supervene earlier than histologic changes, and that BE is an early intermediate stage in the process of EAC.

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Section: Discussionmentioning

confidence: 97%

Transcriptional profiling suggests that Barrett's metaplasia is an early intermediate stage in esophageal adenocarcinogenesis

Wang

Zhan

Yin³

et al. 2006

Oncogene

112

106

View full text Add to dashboard Cite

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“…are also potential candidates to mediate TGFh1-regulated cell death (56), we believe that this is unlikely. TWEAK and other ligands are relatively inefficient inducers of apoptosis (56,57) and there are no reports of their activity in prostate epithelial cells. It is also formally possible that TGFh1 induces multiple extracellular death ligands in NRP cells and blocking any one is not sufficient to inhibit cell death.…”

Section: Discussionmentioning

confidence: 99%

FLICE-Like Inhibitory Protein Blocks Transforming Growth Factor β1–Induced Caspase Activation and Apoptosis in Prostate Epithelial Cells

Nastiuk

Yoo

et al. 2008

Molecular Cancer Research

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Androgen withdrawal induces the regression of human prostate cancers, but such cancers eventually become androgen-independent and metastasize. Thus, deciphering the mechanism of androgen withdrawalinduced apoptosis is critical to designing new therapies for prostate cancer. Previously, we showed that in the rat, castration-induced apoptosis is accompanied by a reduction in the expression of the apical caspase inhibitor FLICE-like inhibitory protein (FLIP). To test the functional role of FLIP in inhibiting prostate epithelial cell apoptosis, we employed the rat prostate epithelial cell line NRP-152, which differentiates to a secretory phenotype in a low-mitogen medium and then undergoes apoptosis following the addition of transforming growth factor B1 (TGFB1), mimicking androgen withdrawal -induced apoptosis. FLIP levels decline with TGFB1 treatment, suggesting that apoptosis is mediated by caspase-8 and indeed the caspase inhibitor crmA blocks TGFB1-induced apoptosis. Small interfering RNA -mediated knockdown of FLIP recapitulates and enhances TGFB1-induced cell death. NRP-152 cells stably transfected with constitutively expressed FLIP were refractory to TGFB1-induced apoptosis. TGFB1-induced caspase-3 activity is proportional to the level of cell death and inversely proportional to the level of FLIP expression in various clones. Moreover, neither caspase-3 nor PARP is cleaved in clones expressing high levels of FLIP. Furthermore, insulin, which inhibits differentiation, increases FLIP and inhibits TGFB-induced death in a FLIP-dependent manner. Although neither Fas-Fc, sTNFRII-Fc, nor DR5-Fc blocked TGFB1-induced cell death, there is a significant increase in tumor necrosis factor mRNA following TGFB stimulation, suggesting both an unexpected role for tumor necrosis factor in this model system and the possibility that FLIP blocks another unknown caspase-dependent mediator of apoptosis. (Mol Cancer Res 2008;6(2):231 -42)

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“…8 -11 TWEAK, a TNF superfamily ligand, and its counter-receptor Fn14 (fibroblast growth factor-inducible 14-kDa protein) are expressed in a range of immune and nonimmune cell types. TWEAK, which is expressed on cells such as macrophages, dendritic cells, NK cells, endothelial cells, microglial cells, and astrocytes, 6,12,13 stimulates proliferation of astrocytes Supported in part by the National Institutes of Health (RO1 AI031044 and RO1CA 074958 to M.L.T. ).…”

mentioning

confidence: 99%

Fn14-TRAIL, a Chimeric Intercellular Signal Exchanger, Attenuates Experimental Autoimmune Encephalomyelitis

Razmara

Hilliard

Ziarani

et al. 2009

The American Journal of Pathology

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Hallmarks of the pathogenesis of autoimmune encephalomyelitis include perivascular infiltration of inflammatory cells into the central nervous system, multifocal demyelination in the brain and spinal cord, and focal neuronal degeneration. Optimal treatment of this complex disease will ultimately call for agents that target the spectrum of underlying pathogenic processes. In the present study, Fn14-TRAIL is introduced as a unique immunotherapeutic fusion protein that is designed to exchange and redirect intercellular signals within inflammatory cell networks, and, in so doing, to impact multiple pathogenic events and yield a net anti-inflammatory effect. In this soluble protein product, a Fn14 receptor component (capable of blocking the pro-inflammatory TWEAK ligand) is fused to a TRAIL ligand (capable of inhibiting activated, pathogenic T cells). Sustained Fn14-TRAIL expression was obtained in vivo using a transposon-based eukaryotic expression vector. Fn14-TRAIL expression effectively prevented chronic, nonremitting, paralytic disease in myelin oligodendrocyte glycoprotein-challenged C57BL/6 mice. Disease suppression in this model was reflected by decreases in the clinical score, disease incidence, nervous tissue inflammation, and Th1, Th2, and Th17 cytokine responses. Significantly, the therapeutic efficacy of Fn14-TRAIL could not be recapitulated simply by administering its component parts (Fn14 and TRAIL) as soluble agents, either alone or in combination. Its functional pleiotropism was manifest in its additional ability to attenuate the enhanced permeability of the blood-brain barrier that typically accompanies autoimmune encephalomyelitis. (Am J Pathol

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TWEAK, a member of the TNF superfamily, is a multifunctional cytokine that binds the TweakR/Fn14 receptor

Cited by 252 publications

References 42 publications

Transcriptional profiling suggests that Barrett's metaplasia is an early intermediate stage in esophageal adenocarcinogenesis

Transcriptional profiling suggests that Barrett's metaplasia is an early intermediate stage in esophageal adenocarcinogenesis

FLICE-Like Inhibitory Protein Blocks Transforming Growth Factor β1–Induced Caspase Activation and Apoptosis in Prostate Epithelial Cells

Fn14-TRAIL, a Chimeric Intercellular Signal Exchanger, Attenuates Experimental Autoimmune Encephalomyelitis

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