The TP53 transcription factor is frequently mutated at later stages of epithelial cancers, indicating a possible role in their invasion and metastasis. Importantly, in most cases rather than a simple loss of function p53 mutation, point mutations of p53 accumulate at the protein level and may have dominant negative functions. This study analyses gene expression differences between mice harbouring p53 mutation who do and do not develop metastasis.
Targeting the LOX/hypoxia axis reverses many of the features that make pancreatic cancer deadly: inhibition of LOX abrogates metastasis and enhances drug efficacy.
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View SamplesEffects of SPRY2 deficiency in gene expression of CWR22Res prostate cancer cells.
No associated publication
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Independence of repressive histone marks and chromatin compaction during senescent heterochromatic layer formation.
Sex, Cell line, Treatment
View SamplesCellular stress responses can be activated following functional defects in organelles such as mitochondria and the endoplasmic reticulum. Mitochondrial dysfunction caused by loss of the serine protease HtrA2 leads to a progressive movement disorder in mice and has been linked to parkinsonian neurodegeneration in humans. Here we demonstrate that loss of HtrA2 results in transcriptional up-regulation of nuclear genes characteristic of the integrated stress response, including the transcription factor CHOP, selectively in the brain. We also show that loss of HtrA2 results in the accumulation of unfolded proteins in the mitochondria, defective mitochondrial respiration and enhanced production of reactive oxygen species that contribute to the induction of CHOP expression and to neuronal cell death. CHOP expression is also significantly increased in Parkinsons disease patients brain tissue. We therefore propose that this brain-specific transcriptional response to stress may be important in the advance of neurodegenerative diseases.
Mitochondrial dysfunction triggered by loss of HtrA2 results in the activation of a brain-specific transcriptional stress response.
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View SamplesCellular stress responses can be activated following functional defects in organelles such as mitochondria and the endoplasmic reticulum. Mitochondrial dysfunction caused by loss of the serine protease HtrA2 leads to a progressive movement disorder in mice and has been linked to parkinsonian neurodegeneration in humans. Here we demonstrate that loss of HtrA2 results in transcriptional up-regulation of nuclear genes characteristic of the integrated stress response, including the transcription factor CHOP, selectively in the brain. We also show that loss of HtrA2 results in the accumulation of unfolded proteins in the mitochondria, defective mitochondrial respiration and enhanced production of reactive oxygen species that contribute to the induction of CHOP expression and to neuronal cell death. CHOP expression is also significantly increased in Parkinsons disease patients brain tissue. We therefore propose that this brain-specific transcriptional response to stress may be important in the advance of neurodegenerative diseases.
Mitochondrial dysfunction triggered by loss of HtrA2 results in the activation of a brain-specific transcriptional stress response.
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View SamplesGM-CSF derived bone marrow cultures contain several subsets of CD11c+MHCII+ mononuclear phagocytes
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Specimen part, Treatment
View SamplesFrequent loss of heterozygosity (LOH) at 11q22-23 in breast cancer strongly suggests that this region contains a tumor suppressor gene, yet to be identified. We and others have shown Yes-associated protein (YAP), which is located at 11q22.2, transactivates the p53 family member p73 upon DNA damage, suggesting a tumor suppressive function for YAP. Our analysis of breast tumor tissues by immunohistochemistry (IHC) showed loss of YAP protein expression in great portion of breast cancers.
No associated publication
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View SamplesThe expansion of repressive epigenetic marks has been implicated in heterochromatin formation during embryonic development, but the general applicability of this mechanism is unclear. Here we show that nuclear rearrangement of repressive histone marks H3K9me3 and H3K27me3 into non-overlapping structural layers characterizes senescence-associated heterochromatic foci (SAHF) formation in human fibroblasts. However, the global landscape of these repressive marks remains unchanged upon SAHF formation, suggesting that in somatic cells heterochromatin can be formed through the spatial repositioning of pre-existing repressively marked histones. This model is reinforced by the correlation of pre-senescent replication timing with both the subsequent layered structure of SAHFs and the global landscape of the repressive marks, allowing us to integrate microscopic and genomic information. Furthermore, modulation of SAHF structure does not affect the occupancy of these repressive marks nor vice versa. These experiments reveal that high-order heterochromatin formation and epigenetic remodeling of the genome can be discrete events.
Independence of repressive histone marks and chromatin compaction during senescent heterochromatic layer formation.
Sex, Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Budding yeast Wapl controls sister chromatid cohesion maintenance and chromosome condensation.
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View SamplesCD141+DNGR-1+ cDC1 have a dual origin. Both MLP and CMP can differentiate in CD141+DNGR-1+ cDC1s.
Dendritic Cell Lineage Potential in Human Early Hematopoietic Progenitors.
Specimen part
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