This SuperSeries is composed of the SubSeries listed below.
Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition.
Specimen part, Cell line
View SamplesInhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure.
Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition.
Specimen part
View SamplesWe study the effect of four QTN in RME1, IME1 & RSF1 that are causative for variation in sporulation efficiency. We investigate the relationship between genotype, gene expression and phenotype and whether the amount of gene expression variation explained by the sporulation QTN is predictive of the amount of phenotypic variation explained by them. Overall design: RNA-Seq analysis of 4 replicates each of 16 allele replacement panel strains containing all combinations of the four sporulation QTN after 2 hours in sporulation medium.
Single nucleotide variants in transcription factors associate more tightly with phenotype than with gene expression.
Subject
View SamplesPurpose: We observed protein homeostasis modulations when anc-1 is knocked-down. We wanted to measure changes in gene expression profiles following this manipulation. Methods: We treated wild type (strain N2) or polyQ35-YFP (strain AM140) nematodes, which express toxic aggregative proteins that challenge their protein homeostasis, with anc-1 RNAi until day six of adulthood, and compared their gene expression levels to those of untreated worms. Results: The knockdown of anc-1 leads to modified expression levels of hundreds of genes. There is an enrichment of transcription factors and protein homeostasis modulators, such as E3 ubiquitin ligases. Conclusions: anc-1 regulates protection from toxic aggregative proteins, at least partially, by regulating the expression of genes that encode protein homeostasis factors. Overall design: Wild type strain, three repeats; polyQ35-YFP strain, four repeats. Each repeat has two conditions: untreated (EV), and RNAi toward anc-1.
Gene expression modulation by the linker of nucleoskeleton and cytoskeleton complex contributes to proteostasis.
Cell line, Subject
View SamplesVon Willebrand factor is a paracrine/autocrine regulator of human mesenchymal stem cell adhesion to distressed/apoptotic endothelial cells.
Von willebrand factor increases endothelial cell adhesiveness for human mesenchymal stem cells by activating p38 mitogen-activated protein kinase.
Specimen part
View SamplesBackground. Multiple myeloma (MM) cells depend on the bone marrow (BM) niche for growth and survival. However, the tumor genes regulated by the niche are largely unknown.
Niche-modulated and niche-modulating genes in bone marrow cells.
Disease, Disease stage, Time
View SamplesGene expression profile (GEP) was analyzed in bone marrow (BM) samples from patients with leukemia or leukemic phase of lymphoma at different time points following aspiration. Among numerous changes in GEP evolved over time a discrete subset of > 60 genes exhibited prompt and sustained switch in expression consistently. Similar results were discovered recently in BM samples from patients with multiple myeloma (GSE36036). GEP was also examined in peripheral blood as well as in BM samples depleted of red blood cells (=WBC) and in cultured cells from some of the patients.
Niche-modulated and niche-modulating genes in bone marrow cells.
Specimen part, Disease
View SamplesPhosphatidylcholine transfer protein (PC-TP, a.k.a StarD2) is abundantly expressed in liver and is regulated by PPAR. When fed the synthetic PPAR ligand fenofibrate, Pctp-/- mice exhibited altered lipid and glucose homeostasis. Microarray profiling of liver from fenofibrate fed wild type and Pctp-/- mice revealed differential expression of a broad array of metabolic genes, as well as their regulatory transcription factors. Because its expression controlled the transcriptional activities of both PPAR and HNF4 in cell culture, the broader impact of PC-TP on nutrient metabolism is most likely secondary to its role in fatty acid metabolism.
Regulatory role for phosphatidylcholine transfer protein/StarD2 in the metabolic response to peroxisome proliferator activated receptor alpha (PPARalpha).
Sex, Age, Specimen part
View SamplesHow animals coordinate gene expression in response to starvation is an outstanding problem closely linked to aging, obesity, and cancer. Newly hatched Caenorhabditis elegans respond to food deprivation by halting development and promoting long-term survival (L1 diapause), thereby providing an excellent model to study starvation response. Through a genetic search, we have discovered that the tumor suppressor Rb critically promotes survival during L1 diapause and likely does so by regulating the expression of genes in both insulin-IGF-1 signaling (IIS)-dependent and -independent pathways mainly in neurons and the intestine. Global gene expression analyses suggested that Rb maintains the starvation-induced transcriptome and represses the re-feeding induced transcriptome, including the repression of many pathogen/toxin/oxidative stress-inducible and metabolic genes, as well as the activation of many other stress-resistant genes, mitochondrial respiratory chain genes, and potential IIS receptor antagonists. Notably, the majority of genes dysregulated in starved L1 Rb(-) animals were not found to be dysregulated in fed conditions. Together, these findings identify Rb as a critical regulator of the starvation response and suggest a link between functions of tumor suppressors and starvation survival. These results may provide mechanistic insights into why cancer cells are often hypersensitive to starvation treatment.
The tumor suppressor Rb critically regulates starvation-induced stress response in C. elegans.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Expression profiling associates blood and brain glucocorticoid receptor signaling with trauma-related individual differences in both sexes.
Sex, Specimen part
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