Filters
Technology
Platform
GSE69915
Homo sapiens
5 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
The Fra-1 transcription factor promotes tumor cell growth, invasion and metastasis. While characterizing five breast cancer cell lines derived from primary human breast tumors, we identified BRC-31 as a novel basal-like cell model that expresses elevated Fra-1 levels. BRC-31 cells display elevated FAK, SRC and ERK2 phosphorylation relative to luminal breast cancer models. Inhibition of this signaling axis, through the use of pharmacological inhibitors, reduces the phosphorylation and stabilization of Fra-1. Elevated integrin V3 expression in these cells suggested that integrin receptors might activate this FAK-SRC-ERK2 signaling axis to enhance Fra-1 phosphorylation. These cells also express high levels of uPAR, a GPI-anchored receptor that has been shown to enhance integrin-mediated signaling initiated by Vitronectin engagement. Transient knockdown of uPAR in BRC31 cells grown on Vitronectin reduces Fra-1 phosphorylation and stabilization and uPAR and Fra-1 are required for Vitronectin-induced cell invasion. In clinical samples, a molecular component signature consisting of Vitronectin-uPAR-uPA-Fra-1 predicts poor overall survival in patients with breast cancer and correlates with a Fra-1 transcriptional signature. Taken together, we have identified a novel-signaling axis that leads to phosphorylation and stabilization of Fra-1, a transcription factor that is emerging as an important modulator of breast cancer progression and metastasis.
Publication Title
Integrin-uPAR signaling leads to FRA-1 phosphorylation and enhanced breast cancer invasion.
Sample Metadata Fields
Age, Disease, Disease stage
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
The loss of E-cadherin causes dysfunction of the cell-cell junction machinery, which is an initial step in epithelial-to-mesenchymal transition (EMT), facilitating cancer cell invasion and the formation of metastases. A set of transcriptional repressors of E-cadherin (CDH1) gene expression, including Snail1, Snail2 and Zeb2 mediate E-cadherin down-regulation in breast cancer. However, the molecular mechanisms underlying the control of E-cadherin expression in breast cancer progression remain largely unknown. Here, by using global gene expression approaches, we uncover a novel function for Cdc42 GTPase-activating protein (CdGAP) in the regulation of expression of genes involved in EMT. We found that CdGAP used its proline-rich domain to form a functional complex with Zeb2 to mediate the repression of E-cadherin expression in ErbB2-transformed breast cancer cells. Conversely, knockdown of CdGAP expression led to a decrease of the transcriptional repressors Snail1 and Zeb2, and this correlated with an increase in E-cadherin levels, restoration of cell-cell junctions, and epithelial-like morphological changes. In vivo, loss of CdGAP in ErbB2-transformed breast cancer cells impaired tumor growth and suppressed metastasis to lungs. Finally, CdGAP was highly expressed in basal-type breast cancer cells, and its strong expression correlated with poor prognosis in breast cancer patients. Together, these data support a previously unknown nuclear function for CdGAP where it cooperates in a GAP-independent manner with transcriptional repressors to function as a critical modulator of breast cancer through repression of E-cadherin transcription. Targeting Zeb2-CdGAP interactions may represent novel therapeutic opportunities for breast cancer treatment. Overall design: Total RNA profiles of ErbB2-expressing control mammary tumor explants cells (shCON) and CdGAP-depleted cells (shCdGAP) were generated by deep sequencing, in triplicate, using Illumina HiSEq2000.
Publication Title
The Cdc42/Rac1 regulator CdGAP is a novel E-cadherin transcriptional co-repressor with Zeb2 in breast cancer.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 175 Downloadable Samples
- Illumina HiSeq 2500
Description
Background: Patients with locally advanced or recurrent prostate cancer typically undergo androgen deprivation therapy (ADT), but the benefits are often short-lived, and responses are variable. ADT failure results in castration-resistant prostate cancer (CRPC), that inevitably leads to metastasis. We hypothesized that differences in tumor transcriptional programs may reflect differential responses to ADT and subsequent metastasis. Results: We performed whole transcriptome analysis of 20 patient-matched Pre-ADT biopsies and 20 Post-ADT prostatectomy specimens, and identified two subgroups of patients (high impact and low impact groups) that exhibited distinct transcriptional changes in response to ADT. We found that all patients lost AR-dependent subtype (PCS2) transcriptional signatures. The high impact group maintained the more aggressive subtype (PCS1) signal, while the low impact group more resembled an AR-suppressed (PCS3) subtype. Computational analyses identified transcription factor coordinated groups (TFCGs) enriched in the high impact group network. Leveraging a large public dataset of over 800 metastatic and primary samples, we identified 33 TFCGs in common between high impact group and metastatic lesions, including SOX4/FOXA2/GATA4, ERF/ETV5/ETV3/ELF4, and a TFCG containing JUN, JUNB, JUND, FOS, FOSB, and FOSL1. The majority of metastatic TFCGs were subsets of larger TFCGs in the high impact group network, suggesting refinement of critical TFCGs in prostate cancer progression. Conclusions: We have identified TFCGs associated with pronounced initial transcriptional response to ADT, aggressive signatures, and metastasis. Our findings suggest multiple new hypotheses that could lead to novel combination therapies to prevent development of CRPC following ADT. Overall design: Sequence alignment and gene level expression quantifications were obtained using the STAR read aligner. We obtained an average of 91,077,364 reads (sd: 41,923,139) with a mean transcriptome coverage of 64x (83% mapping to exons).
Publication Title
Identification of the Transcription Factor Relationships Associated with Androgen Deprivation Therapy Response and Metastatic Progression in Prostate Cancer.
Sample Metadata Fields
Disease, Treatment, Race, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Characterization of differential gene expression due to cisplatin resistance in human ovarian cancer spheroids by microarray analysis.
Publication Title
Cisplatin Resistant Spheroids Model Clinically Relevant Survival Mechanisms in Ovarian Tumors.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Pluripotency-related, valproic acid (VPA)-induced genome-wide histone H3 lysine 9 (H3K9) acetylation patterns in embryonic stem cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Gene expression profiles of E14 embryonic stem cells (ESCs) before and after treatment with low levels of the histone deacetylase (HDAC) inhibitors valproic acid (VPA) and sodium butyrate (NaBu).
Publication Title
Pluripotency-related, valproic acid (VPA)-induced genome-wide histone H3 lysine 9 (H3K9) acetylation patterns in embryonic stem cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Gene expression profiles of E14 embryonic stem cells (ESCs) before and after treatment with low levels of the histone deacetylase (HDAC) inhibitor valproic acid (VPA).
Publication Title
Pluripotency-related, valproic acid (VPA)-induced genome-wide histone H3 lysine 9 (H3K9) acetylation patterns in embryonic stem cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Rattus norvegicus
- 55 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptome and metabolome analysis of liver and kidneys of rats chronically fed NK603 Roundup-tolerant genetically modified maize.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 27 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
There is an ongoing debate on the potential toxicity of genetically modified food. The ability of rodent feeding trials to assess the potential toxicity of these products is highly debated since a 2-year study in rats fed NK603 Roundup-tolerant genetically modified maize, treated or not with Roundup during the cultivation, resulted in anatomorphological and blood/urine biochemical changes indicative of liver and kidney structure and functional pathology.
Publication Title
Transcriptome and metabolome analysis of liver and kidneys of rats chronically fed NK603 Roundup-tolerant genetically modified maize.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 28 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
There is an ongoing debate on the potential toxicity of genetically modified food. The ability of rodent feeding trials to assess the potential toxicity of these products is highly debated since a 2-year study in rats fed NK603 Roundup-tolerant genetically modified maize, treated or not with Roundup during the cultivation, resulted in anatomorphological and blood/urine biochemical changes indicative of liver and kidney structure and functional pathology.
Publication Title
Transcriptome and metabolome analysis of liver and kidneys of rats chronically fed NK603 Roundup-tolerant genetically modified maize.
Sample Metadata Fields
Sex, Specimen part
View Samples