A high degree of cell plasticity seems to promote malignant tumour progression, and an epithelial-mesenchymal transition (EMT) is suspected to provide cancer cells with increased cell plasticity for the development of metastasis and therapy resistance. Here, we have tested whether the EMT-induced cancer cell plasticity can be therapeutically exploited and we report the efficient conversion of breast cancer cells, which have undergone an EMT, into post-mitotic adipocytes. Delineation of the molecular pathways underlying such transdifferentiation has motivated a combination therapy with a MEK inhibitor and Rosiglitazone to demonstrate the conversion of invasive cancer cells into adipocytes and the repression of primary tumor invasion and metastasis formation in mouse models of breast cancer. The results indicate the high potential to utilize the increased cell plasticity of invasive cancer cells for differentiation therapy and they raise the possibility to employ pharmacological treatments to interfere with tumor invasion and metastasis. Overall design: Mesenchymal breast cancer cells (MT?ECad) were harvested at six different time-points during trasndifferentiation into terminally differentiated adipocytes (two biological replicates per time-point)
Gain Fat-Lose Metastasis: Converting Invasive Breast Cancer Cells into Adipocytes Inhibits Cancer Metastasis.
Subject, Time
View SamplesCancer cell plasticity facilitates the development of therapy resistance and malignant progression. De-differentiation processes, such as an epithelial-mesenchymal transition (EMT), are known to enhance cellular plasticity. Here, we demonstrate that cancer cell plasticity can be exploited therapeutically by forcing the trans-differentiation of EMT-derived breast cancer cells into post-mitotic and functional adipocytes. Delineation of the molecular pathways underlying such trans-differentiation has motivated a combination therapy with a MEK inhibitor and the anti-diabetic drug Rosiglitazone in various mouse models of murine and human breast cancer in vivo. This combination therapy provokes the conversion of invasive and disseminating cancer cells into post-mitotic adipocytes leading to the repression of primary tumor invasion and metastasis formation Overall design: Py2T long term cells and mesenchymal breast cancer cells (MT?ECad) were harvested at day7 and treated with different inhibitors (two biological replicates per time-point)
Gain Fat-Lose Metastasis: Converting Invasive Breast Cancer Cells into Adipocytes Inhibits Cancer Metastasis.
Specimen part, Treatment, Subject, Time
View SamplesAcute myeloid leukemia (AML) continues to have the lowest survival rates of all leukemias. Therefore, new therapeutic strategies are urgently needed to improve clinical outcomes for AML patients. Here, we report a novel role for Wilms’ tumor 1-associated protein (WTAP) in pathogenesis of AML. We have performed RNA-Seq in K562 cells with knockdown of WTAP to ascertain which genes it regulates. Overall design: We have 2 replicates of total RNA for K562 cells and 2 replicates with WTAP knocked down
WTAP is a novel oncogenic protein in acute myeloid leukemia.
Subject
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The transcriptional regulator Aire binds to and activates super-enhancers.
Sex, Age, Specimen part, Treatment
View SamplesMicroarray profiles of MECs from mice treated with topoisomerase inhibitors
The transcriptional regulator Aire binds to and activates super-enhancers.
Sex, Age, Treatment
View SamplesHigh quality RNA was extracted from the whole seedlings (Combined root and leaf samples) using TRI Reagent (Ambion, Inc. USA) and pooled from 12 independent stressed and non-stressed plant samples separately, and treated with DNase-I (QIAGEN GmbH, Germany). Subsequently, RNA cleanup was carried out using RNeasy Plant Mini Kit (QIAGEN GmbH, Germany) and 5 ug of total RNA from each sample in triplicates were reverse-transcribed to double stranded cDNA using the GeneChipᆴ One-Cycle cDNA Synthesis Kit. The biotin-labelled cRNA was made using the GeneChipᆴ IVT Labelling Kit (Affymetrix, CA, USA). Twenty microgram of cRNA samples was fragmented and out of which which 7.5 ug cRNA were hybridized for 16 hours at 45C to the Affymetrix GeneChipᆴ Rice Genome Array (Santa Clara, CA, USA). After washing and staining with R-phycoerythrin streptavidin in a Fluidics Station, using the Genechipᆴ Fluidics Station 450, the arrays were scanned by the Genechipᆴ 3000 Scanner. The chip images were scanned and extracted using default settings and the CEL files were produced with the Affymetrix GeneChip Operating Software (GCOS 1.2). The resulting .CEL files were imported into the GeneSpring GX 10 (Agilent Technologies Inc, Santa Clara CA) and normalized with the PLIER16 algorithm. The resulting expression values were log2-transformed. Average log signal intensity values of three technical replicates for each sample were used for advance analysis.
Comparative analysis of drought-responsive transcriptome in Indica rice genotypes with contrasting drought tolerance.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The nuclear bile acid receptor FXR is a PKA- and FOXA2-sensitive activator of fasting hepatic gluconeogenesis.
Sex, Specimen part, Treatment
View SamplesIdentified genes deregulated in mouse primary hepatocytes after modulation of expression/activity of FOXA2 and FXR in glucagon or insulin state
The nuclear bile acid receptor FXR is a PKA- and FOXA2-sensitive activator of fasting hepatic gluconeogenesis.
Sex, Specimen part, Treatment
View SamplesAnoxia induces several heat shock proteins and a heat pre-treatment can acclimatize Arabidopsis seedlings to a subsequent anoxic treatment. In this work we analyzed the response of Arabidopsis seedlings to anoxia, heat and a combined heat+anoxia stress. A significant overlapping between the anoxic and heat shock responses has been observed by whole-genome microarray analysis.
The heat-inducible transcription factor HsfA2 enhances anoxia tolerance in Arabidopsis.
Age, Treatment
View SamplesVS94 gene expression at different time-points in SAPI medium in absence and presence of AI-2 was studied.
Temporal regulation of enterohemorrhagic Escherichia coli virulence mediated by autoinducer-2.
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