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SRP144494
Mus musculus
9 Downloadable Samples
NextSeq 500
Description
E-cadherin (E-cad) mediates cell-cell adhesion and has been proposed to suppress both invasion and metastasis. However, invasive ductal cancers retain E-cad expression in the primary tumor, circulating tumor cells, and distant metastases. We recently demonstrated that cancer cell clusters are efficient metastatic seeds. Since clusters organize through cell-cell adhesion, we tested the requirement for E-cad in genetically engineered mouse models of luminal and basal breast cancer. Loss of E-cad increased invasion and dissemination in 3D culture and in the mammary gland. However, E-cad loss also reduced cancer cell proliferation, survival, tumor cell seeding, and metastatic outgrowth in the lungs. At the transcript level, loss of E-cad was associated with increased apoptosis. Consistent with these results, inhibition of apoptosis partially rescued the metastatic phenotype of E-cad null cancer cells. We therefore propose that E-cad is an invasion suppressor, survival factor, and metastasis promoter in invasive ductal cancers. Overall design: Differential gene expression analysis between organoids isolated from adeno-Cre transduced MMTV-PyMT E-cad+/+ (r = 4 biological replicates) and adeno-Cre transduced MMTV-PyMT E-cadfl/fl (r = 5 biological replicates)
Publication Title
E-cadherin is required for metastasis in multiple models of breast cancer.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The tyrosine kinase receptors HER2 and HER3 play an important role in breast cancer. The HER2/HER3 heterodimer is a critical oncogenic unit associated with reduced relapse-free and decreased overall survival. We provide gene expression profile of the mammary epithelial cells MCF10A expressing HER2, HER3 or HER2/HER3 and grown in three-dimensional cultures for 15 days in the presence of heregulin, a known HER3-ligand that stabilizes and activates the HER2/HER3 heterodimer.
Publication Title
Co-expression of HER2 and HER3 receptor tyrosine kinases enhances invasion of breast cells via stimulation of interleukin-8 autocrine secretion.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The Epidermal Growth Factor Receptor 2 (ERBB2 or HER2) is amplified and overexpressed in approximately 20% of invasive breast cancers and is associated with metastasis and poor prognosis. Here we describe the role of a constitutively active splice variant of HER2 (Delta-HER2) in human mammary epithelial cells. Overexpression of Delta-HER2 in human mammary cells decreased apoptosis and increased proliferation and expression of epithelial-to-mesenchymal markers. It also induced invasion in three-dimensional cultures and promoted tumorigenicity and metastasis in vivo. In contrast, similar overexpression of wild-type HER2 failed to evoke the same effects. Unbiased protein-tyrosine phosphorylation profiling revealed a significant increase in phosphorylation of several key signaling proteins upon Delta-HER2 expression, some of which not previously shown to belong to the HER2 pathway. In addition, microarray analysis revealed the expression of a set of genes specifically associated with Delta-HER2 expression. We found those genes to be highly expressed in ER-negative, high grade and metastatic primary breast tumors. Altogether, these results provide new insights into the function of a tumorigenic splice variant of HER2 and the signaling cascade deriving from its activity
Publication Title
Mammary tumor formation and metastasis evoked by a HER2 splice variant.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Tyrosine phosphatase SHP2 promotes breast cancer progression and maintains tumor-initiating cells via activation of key transcription factors and a positive feedback signaling loop.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The first bona fide PTP proto-oncogene was the Src-homology 2 domain-containing phosphatase SHP2 (encoded by PTPN11), an ubiquitously expressed PTP that transduces mitogenic, pro-survival, cell fate and/or pro-migratory signals from numerous growth factor-, cytokine- and extracellular matrix receptors. In malignancies, SHP2 is hyperactivated either downstream of oncoproteins or by mutations.We provide analysis of the breast cancer cells BT474 grown as xenografts in the presence or absence of SHP2 for 30 days.
Publication Title
Tyrosine phosphatase SHP2 promotes breast cancer progression and maintains tumor-initiating cells via activation of key transcription factors and a positive feedback signaling loop.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The first bona fide PTP proto-oncogene was the Src-homology 2 domain-containing phosphatase SHP2 (encoded by PTPN11), an ubiquitously expressed PTP that transduces mitogenic, pro-survival, cell fate and/or pro-migratory signals from numerous growth factor-, cytokine- and extracellular matrix receptors. In malignancies, SHP2 is hyperactivated either downstream of oncoproteins or by mutations.We provide analysis of a primary triple-negative breast tumor grown as xenografts in the presence or absence of SHP2 for 30 days.
Publication Title
Tyrosine phosphatase SHP2 promotes breast cancer progression and maintains tumor-initiating cells via activation of key transcription factors and a positive feedback signaling loop.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The first bona fide PTP proto-oncogene was the Src-homology 2 domain-containing phosphatase SHP2 (encoded by PTPN11), an ubiquitously expressed PTP that transduces mitogenic, pro-survival, cell fate and/or pro-migratory signals from numerous growth factor-, cytokine- and extracellular matrix receptors. In malignancies, SHP2 is hyperactivated either downstream of oncoproteins or by mutations.We provide analysis of the mammary epithelial cells MCF10A overexpressing human HER2 and HER3 and grown in 3D cultures for 15 days in the presence or absence of SHP2.
Publication Title
Tyrosine phosphatase SHP2 promotes breast cancer progression and maintains tumor-initiating cells via activation of key transcription factors and a positive feedback signaling loop.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 35 Downloadable Samples
- NextSeq 500
Description
EMT, Epithelial to mesenchymal transition is a developmental biology process associated with migration, known to be involved in cancer metastasis. To study this process, we used the breast epithelial cell line MCF10A that enter in EMT after treatment with the cytokine TGFB or by expression of EMT transcriptor factor SNAIL. Overall design: mRNA profiles of MCF10A cells treated for 1 or 6 days with TGFb (done in duplicate), and mRNA profiles of Snail inducible line, MCF10A-SNAIl, induced for 1 or 6 days.
Publication Title
Genomic Instability Is Induced by Persistent Proliferation of Cells Undergoing Epithelial-to-Mesenchymal Transition.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2000, Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
We conducted an in vivo genome-wide CRISPR activation screen to identify genes that accelerate distal metastasis by breast cancer patient-derived circulating tumor cells (CTCs) following direct intravascular inoculation in mice. Regulators of translation and ribosomal proteins were prominent among these, and expression of RPL15, a component of the large ribosome subunit, was sufficient to increase metastatic growth in multiple organs. RPL15 overexpression selectively increases translation of other ribosomal proteins and cell cycle regulators. Unsupervised analysis of single-cell RNA sequencing of freshly-isolated CTCs from breast cancer patients identifies a subset with strong ribosomal and protein translation signatures, correlated with increased proliferative markers, epithelial markers and poor clinical outcome. Thus, ribosome protein expression identifies an aggressive subset of CTCs, whose therapeutic targeting may suppress metastatic progression.
Publication Title
Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples