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SRP083902
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- Mus musculus, Homo sapiens
- 40 Downloadable Samples
Affymetrix Mouse Clariom S Array (clariomsmouse), Affymetrix Clariom S Human array (clariomshuman)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
PGC-1α Promotes Breast Cancer Metastasis and Confers Bioenergetic Flexibility against Metabolic Drugs.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 22 Downloadable Samples
- Affymetrix Mouse Clariom S Array (clariomsmouse)
Description
The role of PGC1alpha in breast cancer lung metastasis is largely unknown. We used expression data from lung metastasis of mice injected with PGC1alpha overexpression or control cells to understand global changes that occur upon overexpression of PGC1alpha that lead to lung metastasis.
Publication Title
PGC-1α Promotes Breast Cancer Metastasis and Confers Bioenergetic Flexibility against Metabolic Drugs.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Clariom S Array (clariomsmouse)
Description
The role of PGC1alpha in breast cancer lung metastasis is largely unknown. We used expression data from lung metastatic explants overexpressing PGC1alpha or control, treated with phenformin to understand global gene expression changes which occur in a PGC1alpha context and under phenformin treatment.
Publication Title
PGC-1α Promotes Breast Cancer Metastasis and Confers Bioenergetic Flexibility against Metabolic Drugs.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
To understand global expression changes in a knockdown of PGC1alpha (siPGC1alpha) vs control (siControl) in a lung metastatic cell line (4175)
Publication Title
PGC-1α Promotes Breast Cancer Metastasis and Confers Bioenergetic Flexibility against Metabolic Drugs.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We used microarrays to establish whether EBF1 and Pax5 repress similar or unique genes. We found that EBF1 uniquely represses the expression of the T-lineage transcription factor Gata3.
Publication Title
Transcriptional repression of Gata3 is essential for early B cell commitment.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Reprogrammed somatic cells offer a valuable source of pluripotent cells that have the potential to differentiate into many cells types and provide a new tool for regenerative medicine. In the present study we differentiated induced pluripotent stem cells (iPS cells) into hepatic cells. We first showed that mouse iPS cells could from a complete liver in mouse embryo (E14.5) including hepatocytes, endothelial cells, sinusoidal cells and resident macrophages. We then designed a highly efficient hepatocyte differentiation protocol using defined factors on human embryonic stem cells (ES cells). This protocol was found to generate more than 80% albumin expressing cells that show hepatic functions and express most of liver genes as shown by microarray analyses. Similar results were obtained when human iPS cells were induced to differentiate following the same procedure.
Publication Title
Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Activation or maintenance of a leukemia stem cell self-renewal pathway in downstream myeloid cells is an important component of AML development
Publication Title
The Wnt/beta-catenin pathway is required for the development of leukemia stem cells in AML.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 222 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The tyrosine kinase ErbB2 positive breast tumors have more aggressive tumor growth, poorer clinical outcome, and more resistance to radiotherapy, chemotherapy and hormone therapy. A humanized anti-ErbB2 monoclonal antibody Herceptin and a small molecules inhibitor Lapatinib were developed and approved by FDA to treat patients with ErbB2 amplification and overexpression. Unfortunately, most ErbB2+ breast cancers do not respond to Herceptin and Lapatinib, and the majority of responders become resistant within 12 months of initial therapy (defined as secondary drug resistance). Such differences in response to Lapatinib treatment is contributed by substantial heterogeneity within ErbB2+ breast cancers. To address this possibility, we carried out transcriptomic analysis of mammary tumors from genetically diverse MMTV-ErbB2 mice. This will help us to have a better understanding of the heterogeneous response to ErbB2 targeted therapy and permit us to design better and more individualized (personalized) treatment strategies for human ErbB2 positive breast cancer.
Publication Title
Unraveling heterogeneous susceptibility and the evolution of breast cancer using a systems biology approach.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 55 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
MiRNAs are essential mediators of many biological processes. The aim of this study was to investigate the dynamics of miRNA-mRNA regulatory networks during exercise and subsequent recovery period.
Publication Title
Dynamically regulated miRNA-mRNA networks revealed by exercise.
Sample Metadata Fields
Sex, Age
View Samples