Regulation of TNFR1 and CD95 signalling by receptor compartmentalization

Schütze, Stefan; Tchikov, Vladimir; Schneider-Brachert, Wulf

doi:10.1038/nrm2430

Cited by 270 publications

(234 citation statements)

References 70 publications

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“…The function of TNF a is ambiguous in various cell types because TNF a is mediated by two receptors with different activation paths [53]. The activation of TNF receptor 1 has been reported to decrease MSC growth factor production [54], generate reactive oxygen species, and induce apoptosis [55] whereas TNF receptor 2 has been demonstrated to enhance MSC growth through the activation of NF-jB [56]. Conversely, it has been shown that fetal and adult MSCs are killed by different pathways; in particular, fetal MSCs are preferably killed via TNF a while the adult MSCs are more sensitive to FasL pathway [57].…”

Section: Discussionmentioning

confidence: 99%

Dedifferentiation-Reprogrammed Mesenchymal Stem Cells with Improved Therapeutic Potential

et al. 2011

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Stem cell transplantation has been shown to improve functional outcome in degenerative and ischemic disorders. However, low in vivo survival and differentiation potential of the transplanted cells limits their overall effectiveness and thus clinical usage. Here we show that, after in vitro induction of neuronal differentiation and dedifferentiation, on withdrawal of extrinsic factors, mesenchymal stem cells (MSCs) derived from bone marrow, which have already committed to neuronal lineage, revert to a primitive cell population (dedifferentiated MSCs) retaining stem cell characteristics but exhibiting a reprogrammed phenotype distinct from their original counterparts. Of therapeutic interest, the dedifferentiated MSCs exhibited enhanced cell survival and higher efficacy in neuronal differentiation compared to unmanipulated MSCs both in vitro and in vivo, with significantly improved cognition function in a neonatal hypoxic-ischemic brain damage rat model. Increased expression of bcl-2 family proteins and micro-RNA-34a appears to be the important mechanism giving rise to this previously undefined stem cell population that may provide a novel treatment strategy with improved therapeutic efficacy.

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Section: Discussionmentioning

confidence: 99%

Dedifferentiation-Reprogrammed Mesenchymal Stem Cells with Improved Therapeutic Potential

et al. 2011

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“…However, in the past decade it has become apparent that internalization and intracellular trafficking of receptors also can have a stimulatory role in certain signaling pathways. Internalization and compartmentalization of TNFR1 and Fas following ligand binding may have a key role in directing signal transduction (Schutze et al, 2008). Clathrin-mediated endocytosis of TNFR1 and Fas has been shown to be required for apoptosis stimulation, but not for activation of the NF-kB and MAPK pathways.…”

Section: Recent Advances In Understanding Apoptosis Initiationmentioning

confidence: 99%

New insights into apoptosis signaling by Apo2L/TRAIL

2010

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“…Fas-associated death domain protein (Schu¨tze et al, 2008), which in turn recruits and aggregates several molecules of caspase-8, thereby promoting its autoprocessing and activation. Activation of caspase-8 processes other effector caspase members, including caspase-3 and caspase-7 to initiate a caspase cascade.…”

Section: T-box Transcription Factor 5 In Colon Cancer J Yu Et Almentioning

confidence: 99%

Epigenetic inactivation of T-box transcription factor 5, a novel tumor suppressor gene, is associated with colon cancer

Cheung

et al. 2010

Oncogene

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T-box transcription factor 5 (TBX5) is a member of a phylogenetically conserved family of genes involved in the regulation of developmental processes. The function of TBX5 in cancer development is largely unclear. We identified that TBX5 was preferentially methylated in cancer using methylation-sensitive arbitrarily primed PCR. We aim to clarify the epigenetic inactivation, biological function and clinical significance of TBX5 in colon cancer. Promoter methylation was evaluated by combined bisulfite restriction analysis and bisulfite genomic sequencing. Cell proliferation was examined by cell viability assay and colony formation assay, apoptosis by flow cytometry and cell migration by wound-healing assay. TBX5 target genes were identified by cDNA microarray analysis. Cox regression model and log-rank test were used to identify independent predictors of prognosis. TBX5 was silenced or downregulated in 88% (7/8) colon cancer cell lines, but was expressed in normal colon tissues. Loss of gene expression was associated with promoter methylation. The biological function of TBX5 in human colon cancer cells was examined. Re-expression of TBX5 in silenced colon cancer cell lines suppressed colony formation (Po0.001), proliferation (Po0.001), migration and induced apoptosis (Po0.01). Induction of apoptosis was mediated through cross-talk of extrinsic apoptosis pathway, apoptotic BCL2-associated X protein and Granzyme A signaling cascades. TBX5 suppressed tumor cell proliferation and metastasis through the upregulation of cyclin-dependent kinase inhibitor 2A, metastasis suppressor 1 and downregulation of synuclein gamma and metastasis-associated protein 1 family member 2. TBX5 methylation was detected in 68% (71/105) of primary colon tumors. Multivariate analysis showed that patients with TBX5 methylation had a significantly poor overall survival (P ¼ 0.0007). In conclusion, we identified a novel functional tumor suppressor gene TBX5 inactivated by promoter methylation in colon cancer. Detection of methylated TBX5 may serve as a potential biomarker for the prognosis of this malignancy.

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Regulation of TNFR1 and CD95 signalling by receptor compartmentalization

Cited by 270 publications

References 70 publications

Dedifferentiation-Reprogrammed Mesenchymal Stem Cells with Improved Therapeutic Potential

Dedifferentiation-Reprogrammed Mesenchymal Stem Cells with Improved Therapeutic Potential

New insights into apoptosis signaling by Apo2L/TRAIL

Epigenetic inactivation of T-box transcription factor 5, a novel tumor suppressor gene, is associated with colon cancer

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