TWEAK-induced alternative NF-κB signaling regulates Cxcl10 and Mymx to promote myoblast-to-myotube fusion
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE268411 | GEO | 2026/03/03
REPOSITORIES: GEO
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Project description:The study aims at illustrate novel role of TWEAK/Fn14 signaling in synapse function by combining electrophysiological and phosphoproteomic approaches. The results show that TWEAK acutely dampens basal synaptic transmission and plasticity through neuronal Fn14 and impacts the phosphorylation state of pre- and post-synaptic proteins in adult mouse hippocampal slices. Two models featuring synaptic deficits were used in the study. Blocking TWEAK/Fn14 signaling augments synaptic function in hippocampal slices from amyloid beta-overexpressing mice. After stroke, genetic or pharmacological inhibition of TWEAK/Fn14 signaling augments basal synaptic transmission and normalizes plasticity. Our data support a glial/neuronal axis that critically modifies synaptic physiology and pathophysiology in different contexts in the mature brain and may be a therapeutic target for improving neurophysiological outcomes.
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Project description:Tumor necrosis factor-related weak inducer of apoptosis, TWEAK, is a TNF superfamily member that mediates signaling through its receptor fibroblast growth factor inducible-14, Fn14. In tumor cell lines, TWEAK induces proliferation, survival and NF-kappaB signaling and gene expression that promote tumor growth and suppress antitumor immune responses. Anti-TWEAK antibody, RG7212, inhibits tumor growth in vivo with decreases in pathway activation markers and modulation of tumor, blood and spleen immune cell composition. Candidate response prediction markers, including Fn14, have been identified in mouse models. Phase I pharmacodynamic data from patients are consistent with preclinical results. TWEAK:Fn14 signaling is upregulated in human cancer and pathway activation induces tumor proliferation and survival signaling. Blockade with anti-TWEAK mAb, RG7212, inhibits tumor growth in multiple models in mice. TWEAK induces changes that suppress anti-tumor immune responses and RG7212 blocks these effects resulting in changes in tumor immune cell composition and decreases in cytokines that promote immunosuppression. Antitumor efficacy in mice was observed in a range of Fn14 expressing models with pathway activation and expressing either wild-type or mutant p53, BRAF or KRAS suggesting both a patient selection strategy and potential broad clinical applicability. Preclinical mechanism of action hypotheses are supported by Phase I clinical data, with decreases in proliferation markers and increased tumor T cell infiltration. U2OS cells untreated or treated with 1090-TW (TWEAK) for 15 minutes, 1 hour, 4 hours, 8 hours, or 24 hours. Five replicates for each condition were performed.
2013-10-04 | E-GEOD-41828 | biostudies-arrayexpress
Project description:Tumor necrosis factor-related weak inducer of apoptosis, TWEAK, is a TNF superfamily member that mediates signaling through its receptor fibroblast growth factor inducible-14, Fn14. In tumor cell lines, TWEAK induces proliferation, survival and NF-kappaB signaling and gene expression that promote tumor growth and suppress antitumor immune responses. Anti-TWEAK antibody, RG7212, inhibits tumor growth in vivo with decreases in pathway activation markers and modulation of tumor, blood and spleen immune cell composition. Candidate response prediction markers, including Fn14, have been identified in mouse models. Phase I pharmacodynamic data from patients are consistent with preclinical results. TWEAK:Fn14 signaling is upregulated in human cancer and pathway activation induces tumor proliferation and survival signaling. Blockade with anti-TWEAK mAb, RG7212, inhibits tumor growth in multiple models in mice. TWEAK induces changes that suppress anti-tumor immune responses and RG7212 blocks these effects resulting in changes in tumor immune cell composition and decreases in cytokines that promote immunosuppression. Antitumor efficacy in mice was observed in a range of Fn14 expressing models with pathway activation and expressing either wild-type or mutant p53, BRAF or KRAS suggesting both a patient selection strategy and potential broad clinical applicability. Preclinical mechanism of action hypotheses are supported by Phase I clinical data, with decreases in proliferation markers and increased tumor T cell infiltration. Pan02 cells untreated or treated with 1090-TW (TWEAK) for 4 hours, 8 hours, or 24 hours. Four replicates for each condition were performed.
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Project description:Tumor necrosis factor-related weak inducer of apoptosis, TWEAK, is a TNF superfamily member that mediates signaling through its receptor fibroblast growth factor inducible-14, Fn14. In tumor cell lines, TWEAK induces proliferation, survival and NF-kappaB signaling and gene expression that promote tumor growth and suppress antitumor immune responses. Anti-TWEAK antibody, RG7212, inhibits tumor growth in vivo with decreases in pathway activation markers and modulation of tumor, blood and spleen immune cell composition. Candidate response prediction markers, including Fn14, have been identified in mouse models. Phase I pharmacodynamic data from patients are consistent with preclinical results. TWEAK:Fn14 signaling is upregulated in human cancer and pathway activation induces tumor proliferation and survival signaling. Blockade with anti-TWEAK mAb, RG7212, inhibits tumor growth in multiple models in mice. TWEAK induces changes that suppress anti-tumor immune responses and RG7212 blocks these effects resulting in changes in tumor immune cell composition and decreases in cytokines that promote immunosuppression. Antitumor efficacy in mice was observed in a range of Fn14 expressing models with pathway activation and expressing either wild-type or mutant p53, BRAF or KRAS suggesting both a patient selection strategy and potential broad clinical applicability. Preclinical mechanism of action hypotheses are supported by Phase I clinical data, with decreases in proliferation markers and increased tumor T cell infiltration. ACHN cells untreated or treated with 1090-TW (TWEAK) for 4 hours, 8 hours, or 24 hours. Four replicates for each condition were performed.
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Project description:TWEAK-induced alternative NF-κB signaling regulates Cxcl10 and Mymx to promote myoblast-to-myotube fusion
| PRJNA1117059 | ENA
Project description:TWEAK, also known as TNFSF12, is a multifunctional cytokine that controls many cellular activities in tissue repair and disease by binding to its receptor Fn14.TWEAK-Fn14 signaling has been shown to induce canonical and noncanonical NFkB signaling, triggering pro-inflammatory responses and leukocyte infiltration.We found that TWEAK-Fn14 signaling was upregulated in IPF while Fn14 was mainly expressed in fibroblasts. Therefore, we added different concentrations of TWEAK to primary mouse lung fibroblasts to activate the TWEAK-Fn14 signaling pathway, and explored the transcriptome changes of TWEAK-Fn14 signaling pathway activation in fibroblasts by RNA-seq technology.
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Project description:Tumor necrosis factor-related weak inducer of apoptosis, TWEAK, is a TNF superfamily member that mediates signaling through its receptor fibroblast growth factor inducible-14, Fn14. In tumor cell lines, TWEAK induces proliferation, survival and NF-kappaB signaling and gene expression that promote tumor growth and suppress antitumor immune responses. Anti-TWEAK antibody, RG7212, inhibits tumor growth in vivo with decreases in pathway activation markers and modulation of tumor, blood and spleen immune cell composition. Candidate response prediction markers, including Fn14, have been identified in mouse models. Phase I pharmacodynamic data from patients are consistent with preclinical results. TWEAK:Fn14 signaling is upregulated in human cancer and pathway activation induces tumor proliferation and survival signaling. Blockade with anti-TWEAK mAb, RG7212, inhibits tumor growth in multiple models in mice. TWEAK induces changes that suppress anti-tumor immune responses and RG7212 blocks these effects resulting in changes in tumor immune cell composition and decreases in cytokines that promote immunosuppression. Antitumor efficacy in mice was observed in a range of Fn14 expressing models with pathway activation and expressing either wild-type or mutant p53, BRAF or KRAS suggesting both a patient selection strategy and potential broad clinical applicability. Preclinical mechanism of action hypotheses are supported by Phase I clinical data, with decreases in proliferation markers and increased tumor T cell infiltration. MDA-MB-436 cells untreated or treated with 1090-TW (TWEAK) for 15 minutes, 1 hour, 4 hours, 8 hours, or 24 hours. Five replicates for each condition were performed.
2013-10-04 | E-GEOD-42045 | biostudies-arrayexpress
Project description:Tumor necrosis factor-related weak inducer of apoptosis, TWEAK, is a TNF superfamily member that mediates signaling through its receptor fibroblast growth factor inducible-14, Fn14. In tumor cell lines, TWEAK induces proliferation, survival and NF-kappaB signaling and gene expression that promote tumor growth and suppress antitumor immune responses. Anti-TWEAK antibody, RG7212, inhibits tumor growth in vivo with decreases in pathway activation markers and modulation of tumor, blood and spleen immune cell composition. Candidate response prediction markers, including Fn14, have been identified in mouse models. Phase I pharmacodynamic data from patients are consistent with preclinical results. TWEAK:Fn14 signaling is upregulated in human cancer and pathway activation induces tumor proliferation and survival signaling. Blockade with anti-TWEAK mAb, RG7212, inhibits tumor growth in multiple models in mice. TWEAK induces changes that suppress anti-tumor immune responses and RG7212 blocks these effects resulting in changes in tumor immune cell composition and decreases in cytokines that promote immunosuppression. Antitumor efficacy in mice was observed in a range of Fn14 expressing models with pathway activation and expressing either wild-type or mutant p53, BRAF or KRAS suggesting both a patient selection strategy and potential broad clinical applicability. Preclinical mechanism of action hypotheses are supported by Phase I clinical data, with decreases in proliferation markers and increased tumor T cell infiltration. CAKI cells impanted as xenografts in Athymic, Nu/Nu nude mice, treated with anti-TWEAK antibody (TW212) or Vehicle for 24 hours. Four replicates for each condition were performed. RNA was extracted from xenografts, processed and hybridized to human and mouse chips.
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Project description:Tumor necrosis factor-related weak inducer of apoptosis, TWEAK, is a TNF superfamily member that mediates signaling through its receptor fibroblast growth factor inducible-14, Fn14. In tumor cell lines, TWEAK induces proliferation, survival and NF-kappaB signaling and gene expression that promote tumor growth and suppress antitumor immune responses. Anti-TWEAK antibody, RG7212, inhibits tumor growth in vivo with decreases in pathway activation markers and modulation of tumor, blood and spleen immune cell composition. Candidate response prediction markers, including Fn14, have been identified in mouse models. Phase I pharmacodynamic data from patients are consistent with preclinical results. TWEAK:Fn14 signaling is upregulated in human cancer and pathway activation induces tumor proliferation and survival signaling. Blockade with anti-TWEAK mAb, RG7212, inhibits tumor growth in multiple models in mice. TWEAK induces changes that suppress anti-tumor immune responses and RG7212 blocks these effects resulting in changes in tumor immune cell composition and decreases in cytokines that promote immunosuppression. Antitumor efficacy in mice was observed in a range of Fn14 expressing models with pathway activation and expressing either wild-type or mutant p53, BRAF or KRAS suggesting both a patient selection strategy and potential broad clinical applicability. Preclinical mechanism of action hypotheses are supported by Phase I clinical data, with decreases in proliferation markers and increased tumor T cell infiltration. ACHN cells impanted as xenografts in Athymic, Nu/Nu nude mice, treated with anti-TWEAK antibody (TW212), B20 antibody control or Vehicle for 4 hours, 8 hours, or 24 hours. Five replicates for each condition were performed.
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