A distinct type of macrophages helps breast cancer cells to overcome rate-limiting steps in the metastatic process and establish lethal metastatic tumors. Since only a minor population of cancer cells can establish macroscopic metastatic tumors, we hypothesized that this metastatic cancer cell population have higher expression of receptors for macrophage-derived ligands compared to their parental cells.
Mammary Tumor Cells with High Metastatic Potential Are Hypersensitive to Macrophage-Derived HGF.
Specimen part
View SamplesEndocrine therapy is the main therapeutic option for patients with estrogen receptor alpha positive (ER+) breast cancer. Nevertheless, most of them become estrogen-independent and relapse after the treatment. Ret is a tyrosine kinase receptor that shows elevated expression levels in ER+ human breast tumors. In this study, we demonstrate that activation of the Ret receptor promotes proliferation as well as cell migration irrespective of endocrine therapy. Microarray data show that Ret activation involves changes in the expression of inflammatory- and motility-related genes. In vivo treatment with a Ret pathway inhibitor in a ER+/Ret+ mouse mammary cancer model, reduces tumor growth and lung metastasis even after endocrine therapy. Additionally, we show a connection between Ret and inflammatory pathways. The pro-inflamatory cytokine IL6 lies at the core of this regulation, which involves a positive feedback loop with IL6 and the Ret pathway reciprocally stimulating each other to further leading metastasis risk. Our findings provide insight into endocrine resistance mechanism and point at the Ret pathway as a potential target for future therapies.
Ret inhibition decreases growth and metastatic potential of estrogen receptor positive breast cancer cells.
Cell line, Treatment, Time
View SamplesMM1.S cells stably transduced with control or b-catenin shRNA were established. Total RNA was isolated from 5x 10^6 cells of each in triplicate.
Aurora kinase A is a target of Wnt/beta-catenin involved in multiple myeloma disease progression.
Cell line
View SamplesThis GEO submission includes RNAseq raw data (fastq) and processed data (using ASpli 1.6.0) from samples obtained in the wild type and the single prefoldin4 and lsm8 mutants in three different environmental conditions as well as in the triple prefoldin2 prefoldin4 prefoldin6 mutant growth in standard conditions. Overall design: 28 biological samples from 10 different conditions and genopypes, including the Col-0 WT in each condition (standard, cold and salt conditions)
Prefoldins contribute to maintaining the levels of the spliceosome LSM2-8 complex through Hsp90 in Arabidopsis.
Specimen part, Subject
View SamplesStabilized Alpha-Helix peptides of BCL9 HD2 (SAH-BCL9) block BCL9 and B9L interactions with beta-catenin and specifically downregulate Wnt target gene expression.
Targeted disruption of the BCL9/β-catenin complex inhibits oncogenic Wnt signaling.
Specimen part, Cell line, Treatment
View SamplesMultiple myeloma (MM) evolves from highly prevalent premalignant condition termed Monoclonal Gammopathy of Undetermined Significance (MGUS). We report an MGUS-MM phenotype arising in transgenic mice with Emu-directed expression of the unfolded protein/ER stress response and plasma cell development spliced isoform factor XBP-1s. Emu-XBP-1s elicited elevated serum Ig and IL-6 levels, skin alterations and with advancing age, a significant proportion of Emu-xbp-1s transgenic mice develop features diagnostic of human MM including bone lytic lesions. Transcriptional profiles of Emu-xbp-1s B lymphoid and MM cells show aberrant expression of genes known to be dysregulated in human MM including Cyclin D1, MAF, MAFB, and APRIL. This genetic model coupled with documented frequent XBP-1s overexpression in human MM serve to implicate chronic XBP-1s dysregulation in the development of this common and lethal malignancy.
The differentiation and stress response factor XBP-1 drives multiple myeloma pathogenesis.
No sample metadata fields
View SamplesBoth microRNAs and alternative pre-mRNA splicing have been implicated in the development of the nervous system (NS), but functional interactions between these two pathways are poorly understood. We demonstrate that the neuron-specific microRNA miR-124a directly targets PTBP1/PTB/hnRNPI mRNA, which encodes a global repressor of alternative pre-mRNA splicing in non-neuronal cells. Among the targets of PTBP1 is a critical cassette exon in the pre-mRNA of PTBP2/nPTB/brPTB, an NS-enriched PTBP1 homolog. When this exon is skipped, PTBP2 mRNA is subject to nonsense-mediated decay. During neuronal differentiation, miR-124a reduces PTBP1 levels leading to the accumulation of correctly spliced PTBP2 mRNA and a dramatic increase in PTBP2 protein. These events culminate in the transition from non-NS to NS-specific alternative splicing patterns. We also present evidence that miR-124a plays a key role in the differentiation of progenitor cells to mature neurons. Thus, miR-124a promotes NS development at least in part by regulating an intricate network of NS-specific alternative splicing.
The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing.
No sample metadata fields
View Samplesp63 is critical for epithelial development yet little is known about the transcriptional programmes it regulates. The p63 transactivating (TA) isoforms contain an amino-terminal exon that encodes a p53-like transactivation domain, whereas N-isoforms lack this domain but contain the common DNA binding domain (DBD), suggesting that TAp63 and Np63 isoforms may have opposing functions. By characterising transcriptional changes and cellular effects following modulation of p63 expression, we have defined a vital role for p63 in cellular adhesion. Knockdown of p63 expression caused downregulation of cell adhesion-associated genes, cell detachment and anoikis in mammary epithelial cells and keratinocytes. Conversely, overexpression of the TAp63 or Np63 isoforms of p63 upregulated cell adhesion molecules, increased cellular adhesion and conferred resistance to anoikis.
p63 regulates an adhesion programme and cell survival in epithelial cells.
Cell line
View SamplesWe used microarrays to unveil the gene expression alterations upon short-term HFD administration
Dietary alterations modulate susceptibility to Plasmodium infection.
Specimen part
View SamplesParthenogenetic stem cells were derived from parthenotes, then differentiated to mesenchymal stem cells. These were further reprogrammed to induced pluripotent stem cells, which were finally differentiated to secondary mesenchymal stem cells.
Accumulation of instability in serial differentiation and reprogramming of parthenogenetic human cells.
Sex, Specimen part
View Samples