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GSE52246
Homo sapiens
8 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Cellular plasticity confers cancer cells the ability to adapt to micro-environmental changes, a fundamental requirement for tumour progression and metastasis. The epithelial to mesenchymal transition (EMT) is a transcriptional programme associated with increased cell motility and stemness. Beside EMT, the mesenchymal to amoeboid transition (MAT) has been described during tumour progression but, to date, little is known about its transcriptional control and involvement in stemness. The aim of this study is to investigate (i) the transcriptional profile associated with the MAT programme and (ii) to study whether MAT acquisition in melanoma cancer cells correlate with clonogenic potential to promote tumor growth. Our results demonstrate that MAT programme in melanoma is characterised by increased stemness and clonogenic features of cancer cells, thus sustaining tumour progression. Furthermore, these data suggest that stemness is not an exclusive feature of cells undergoing EMT, but more generally is associated with an increase in cellular plasticity of cancer cells.
Publication Title
Mesenchymal to amoeboid transition is associated with stem-like features of melanoma cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrated gene and miRNA expression analysis of prostate cancer associated fibroblasts supports a prominent role for interleukin-6 in fibroblast activation.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Tumor microenvironment coevolves with and simultaneously sustains cancer progression. Reactive fibroblasts found in prostate cancer (PCa), known as cancer associated fibroblasts (CAF), have been indeed shown to fuel tumor development and metastasis by mutually interacting with PCa cells. Little is known about the molecular mechanisms that lead to activation of CAFs from tissue-resident fibroblasts, circulating marrow-derived fibroblast progenitors or mesenchymal stem cells. Through integrated gene and microRNA expression profiling, here we showed that transcriptome of CAFs isolated from prostate tumors strictly resembles that of normal fibroblasts stimulated in vitro with interleukin-6 (IL6), thus confirming the capability of the cytokine to promote acquisition of an activated and cancer-promoting phenotype, and, for the first time, proving that IL6 is able per se to induce all the complex transcriptional changes characteristic of patient-derived CAFs. Comparison with publicly available datasets, however, suggested that prostate CAFs may be alternatively characterized by IL6 and TGF-related signatures, indicating that either signal, depending on the context, tumor stage and etiology, may concur to fibroblast activation. Our analyses also highlighted pathways relevant for induction of reactive stroma, including genes the role of which in fibroblast activation is still to be explored. In addition, we revealed a role for muscle-specific miR-133b as a soluble factor secreted by activated fibroblasts to support paracrine activation of non-activated fibroblasts or promote tumor progression. Overall, in this study we provided insights on the molecular mechanisms driving fibroblast activation in prostate cancer, thus contributing to identify novel hits for the development of therapeutic strategies targeting the crucial interplay between tumor cells and their microenvironment. Tumor microenvironment coevolves with and simultaneously sustains cancer progression. Reactive fibroblasts found in prostate cancer (PCa), known as cancer associated fibroblasts (CAF), have been indeed shown to fuel tumor development and metastasis by mutually interacting with PCa cells. Little is known about the molecular mechanisms that lead to activation of CAFs from tissue-resident fibroblasts, circulating marrow-derived fibroblast progenitors or mesenchymal stem cells. Through integrated gene and microRNA expression profiling, here we showed that transcriptome of CAFs isolated from prostate tumors strictly resembles that of normal fibroblasts stimulated in vitro with interleukin-6 (IL6), thus confirming the capability of the cytokine to promote acquisition of an activated and cancer-promoting phenotype, and, for the first time, proving that IL6 is able per se to induce all the complex transcriptional changes characteristic of patient-derived CAFs. Comparison with publicly available datasets, however, suggested that prostate CAFs may be alternatively characterized by IL6 and TGF-related signatures, indicating that either signal, depending on the context, tumor stage and etiology, may concur to fibroblast activation. Our analyses also highlighted pathways relevant for induction of reactive stroma, including genes the role of which in fibroblast activation is still to be explored. In addition, we revealed a role for muscle-specific miR-133b as a soluble factor secreted by activated fibroblasts to support paracrine activation of non-activated fibroblasts or promote tumor progression. Overall, in this study we provided insights on the molecular mechanisms driving fibroblast activation in prostate cancer, thus contributing to identify novel hits for the development of therapeutic strategies targeting the crucial interplay between tumor cells and their microenvironment. Tumor microenvironment coevolves with and simultaneously sustains cancer progression. Reactive fibroblasts found in prostate cancer (PCa), known as cancer associated fibroblasts (CAF), have been indeed shown to fuel tumor development and metastasis by mutually interacting with PCa cells. Little is known about the molecular mechanisms that lead to activation of CAFs from tissue-resident fibroblasts, circulating marrow-derived fibroblast progenitors or mesenchymal stem cells. Through integrated gene and microRNA expression profiling, here we showed that transcriptome of CAFs isolated from prostate tumors strictly resembles that of normal fibroblasts stimulated in vitro with interleukin-6 (IL6), thus confirming the capability of the cytokine to promote acquisition of an activated and cancer-promoting phenotype, and, for the first time, proving that IL6 is able per se to induce all the complex transcriptional changes characteristic of patient-derived CAFs. Comparison with publicly available datasets, however, suggested that prostate CAFs may be alternatively characterized by IL6 and TGF-related signatures, indicating that either signal, depending on the context, tumor stage and etiology, may concur to fibroblast activation. Our analyses also highlighted pathways relevant for induction of reactive stroma, including genes the role of which in fibroblast activation is still to be explored. In addition, we revealed a role for muscle-specific miR-133b as a soluble factor secreted by activated fibroblasts to support paracrine activation of non-activated fibroblasts or promote tumor progression. Overall, in this study we provided insights on the molecular mechanisms driving fibroblast activation in prostate cancer, thus contributing to identify novel hits for the development of therapeutic strategies targeting the crucial interplay between tumor cells and their microenvironment.
Publication Title
Integrated gene and miRNA expression analysis of prostate cancer associated fibroblasts supports a prominent role for interleukin-6 in fibroblast activation.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Gene expression profiling of cultured skin fibroblasts obtained from patients affected with classical Ehlers Danlos syndrome (cEDS)
Publication Title
Molecular insights in the pathogenesis of classical Ehlers-Danlos syndrome from transcriptome-wide expression profiling of patients' skin fibroblasts.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Analysis of gene expression profiling of cultured skin fibroblasts obtained from patients affected with vascular Ehlers Danlos syndrome (vEDS)
Publication Title
Transcriptome analysis of skin fibroblasts with dominant negative COL3A1 mutations provides molecular insights into the etiopathology of vascular Ehlers-Danlos syndrome.
Sample Metadata Fields
Disease
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
To screen for candidate genes that may contribute to the pathogenesis of ATS
Publication Title
GLUT10 deficiency leads to oxidative stress and non-canonical αvβ3 integrin-mediated TGFβ signalling associated with extracellular matrix disarray in arterial tortuosity syndrome skin fibroblasts.
Sample Metadata Fields
Disease
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina HiSeq 2000
Description
Microenvironment is known to influence cancer drug response and sustain resistance to therapies targeting receptor-tyrosine kinases. However if and how tumor microenvironment can be altered during treatment, contributing to resistance onset is not known. Here we show that, under prolonged treatment with tyrosine kinase inhibitors (TKIs), EGFR- or MET-addicted cancer cells displayed a metabolic shift towards increased glycolysis and lactate production. We identified secreted lactate as the key molecule able to instruct Cancer Associated Fibroblasts (CAFs) to produce Hepatocyte Growth Factor (HGF) in a NF-KB dependent manner. Increased HGF, activating MET-dependent signaling in cancer cells, sustained resistance to TKIs. Functional targeting or pharmacological inhibition of lactate dehydrogenase prevented and overcame in vivo resistance, demonstrating the crucial role of this metabolite in the adaptive process. This non-cell-autonomous, adaptive resistance mechanism was observed in NSCLC patients progressed on EGFR TKIs, demonstrating the clinical relevance of our findings and opening novel scenarios in the challenge to drug resistance Overall design: RNA-seq analysis of 2 different samples, each one with 2 biological replicates (4 sequencing runs in total).
Publication Title
Increased Lactate Secretion by Cancer Cells Sustains Non-cell-autonomous Adaptive Resistance to MET and EGFR Targeted Therapies.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptome-Wide Expression Profiling in Skin Fibroblasts of Patients with Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome Hypermobility Type.
Sample Metadata Fields
Disease, Disease stage
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
To unravel the molecular mechanisms potentially associated with the pathogenesis of the EDS-HT/JHS.
Publication Title
Transcriptome-Wide Expression Profiling in Skin Fibroblasts of Patients with Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome Hypermobility Type.
Sample Metadata Fields
Disease, Disease stage
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Acute lymphoblastic leukemia (ALL) is an heterogeneous disease comprising several subentities that differ for both immunophenotypic and molecular characteristics. Over the years, the biologic understanding of this neoplasm has largely increased. Gene expression profiling has recently allowed to identify specific signatures for the different ALL subsets and permitted identification of pathways deregulated by a given lesion. MicroRNAs (miRNAs) are small non-coding RNAs which play a pivotal role in several cellular functions. In this study, we investigated miRNA and gene expression profiles in a series of adult ALL cases by microarray analysis and combined them by bioinformatic analysis. Interestingly, those miRNAs which are differentially expressed between the ALL classes accounted for a large proportion of miRNA/mRNA expression pairs identified by the above analysis. Moreover, the analysis highlighted several putative miRNA targets involved in apoptosis and cell-cycle regulation.
Publication Title
Characterization of B- and T-lineage acute lymphoblastic leukemia by integrated analysis of MicroRNA and mRNA expression profiles.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples