Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA322427 | ENA |
REPOSITORIES: ENA
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Project description:We previously identified a gene signature predicted to regulate the epithelial-mesenchymal transition (EMT) in both epithelial tissue stem cells and breast cancer cells. A phenotypic RNA interference (RNAi) screen identified the genes within this 140-gene signature that promoted the conversion of mesenchymal epithelial cell adhesion molecule-negative (EpCAM-) breast cancer cells to an epithelial EpCAM+/high phenotype. The screen identified 10 of the 140 genes whose individual knockdown was sufficient to promote EpCAM and E-cadherin expression. Among these 10 genes, RNAi silencing of the SWI/SNF chromatin-remodeling factor Smarcd3/Baf60c in EpCAM- breast cancer cells gave the most robust transition from the mesenchymal to epithelial phenotype. Conversely, expression of Smarcd3/Baf60c in immortalized human mammary epithelial cells induced an EMT. The mesenchymal-like phenotype promoted by Smarcd3/Baf60c expression resulted in gene expression changes in human mammary epithelial cells similar to that of claudin-low triple-negative breast cancer cells. These mammary epithelial cells expressing Smarcd3/Baf60c had upregulated Wnt5a expression. Inhibition of Wnt5a by either RNAi knockdown or blocking antibody reversed Smarcd3/Baf60c-induced EMT. Thus, Smarcd3/Baf60c epigenetically regulates EMT by activating WNT signaling pathways. sampleXreference
2013-08-19 | E-GEOD-40145 | biostudies-arrayexpress
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Project description:ABSTRACT: Obesity is responsible for decreased overall survival for breast cancer patients. Here, we describe the generation, characterization and application of a novel murine mammary tumor initiating cell model (M-Wnt) that recapitulates the claudin-low subtype of human breast cancer and permits the study of TIC’s in wild-type, immunocompetent mice. M-Wnt cells readily form mammospheres in suspension culture, express markers consistent with epithelial-to-mesenchymal transition (EMT), and generate claudin-low mammary tumors when as few as 50 cells are orthotopically injected. Using the M-Wnt cell lines in tandem with a more basal-like epithelial breast cancer cell line, E-Wnt, we found that diet induced obesity significantly downregulates epithelial markers, such as E-cadherin, and upregulates mesenchymal markers including fibronectin, N-cadherin, SNAIL, Oct-4, and TGF-b. This reveals a previously unidentified link between energy balance and EMT. The ability of calorie restriction (CR) to reverse EMT, upregulate epithelial markers and downregulate mesenchymal markers indicates the plasticity of the TICs, as well as the potential importance of lifestyle modifications as cancer prevention strategies. 28 array samples
2012-06-29 | E-GEOD-28713 | biostudies-arrayexpress
Project description:We previously identified a gene signature predicted to regulate the epithelial-mesenchymal transition (EMT) in both epithelial tissue stem cells and breast cancer cells. A phenotypic RNA interference (RNAi) screen identified the genes within this 140-gene signature that promoted the conversion of mesenchymal epithelial cell adhesion molecule-negative (EpCAM-) breast cancer cells to an epithelial EpCAM+/high phenotype. The screen identified 10 of the 140 genes whose individual knockdown was sufficient to promote EpCAM and E-cadherin expression. Among these 10 genes, RNAi silencing of the SWI/SNF chromatin-remodeling factor Smarcd3/Baf60c in EpCAM- breast cancer cells gave the most robust transition from the mesenchymal to epithelial phenotype. Conversely, expression of Smarcd3/Baf60c in immortalized human mammary epithelial cells induced an EMT. The mesenchymal-like phenotype promoted by Smarcd3/Baf60c expression resulted in gene expression changes in human mammary epithelial cells similar to that of claudin-low triple-negative breast cancer cells. These mammary epithelial cells expressing Smarcd3/Baf60c had upregulated Wnt5a expression. Inhibition of Wnt5a by either RNAi knockdown or blocking antibody reversed Smarcd3/Baf60c-induced EMT. Thus, Smarcd3/Baf60c epigenetically regulates EMT by activating WNT signaling pathways.
2013-08-19 | GSE40145 | GEO
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2013-11-13 | E-GEOD-52262 | biostudies-arrayexpress
Project description:Tumor cells interact with the microenvironment that specifically supports and promotes tumor development. Key components in the tumor environment have been linked to various aggressive cancer features and can further influence the presence of subpopulations of cancer cells with specific functions, including cancer stem cells and migratory cells. To model and further understand the influence of specific microenvironments we have developed an experimental platform using cell-free patient-derived scaffolds (PDSs) from primary breast cancers infiltrated with standardized breast cancer cell lines. This PDS culture system induced a series of orchestrated changes in differentiation, epithelial-mesenchymal transition, stemness and proliferation of the cancer cell population, where an increased cancer stem cell pool was confirmed using functional assays. Furthermore, global gene expression profiling showed that PDS cultures were similar to xenograft cultures. Mass spectrometry analyses of cell-free PDSs identified subgroups based on their protein composition that were linked to clinical properties, including tumor grade. Finally, we observed that an induction of epithelial-mesenchymal transition-related genes in cancer cells growing on the PDSs were significantly associated with clinical disease recurrences in breast cancer patients. Patient-derived scaffolds thus mimics in vivo-like growth conditions and uncovers unique information about the malignancy-inducing properties of tumor microenvironment.
2020-06-25 | PXD018367 | Pride
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2013-06-14 | E-GEOD-43489 | biostudies-arrayexpress
Project description:It has been suggested that breast cancers are driven and maintained by a cellular subpopulation with stem cell properties. These breast cancer stem cells (BCSCs) mediate metastasis and by virtue of their resistance to radiation and chemotherapy, contribute to relapse. Although several BCSC markers have been described, it is unclear whether these markers identify the same or independent BCSC populations. Based on established breast cancer cell lines, as well as primary tumor samples and xenografts, we show that BCSCs exist in distinct mesenchymal-like (epithelial-mesenchymal transition, EMT) and epithelial-like (mesenchymal-epithelial transition, MET) states characterized by expression of distinct markers, proliferative capacity and invasive characteristics. The gene expression profiles of mesenchymal-like and epithelial-like BCSCs are remarkably similar across the different molecular subtypes of breast cancer and resemble those of distinct basal and luminal stem cells found in the normal breast. We propose that the plasticity of BCSCs allowing them to transition between EMT- and MET-like states endows these cells with the capacity for tissue invasion, dissemination and growth at metastatic sites. Breast cancer cells from patient were sorted using flow cytometry to select for cells that were ALDH+. Gene expression profiles of these cells were compared with profiles of ALDH- cells.
2013-11-14 | E-GEOD-52327 | biostudies-arrayexpress
Project description:The ability of breast cancer cells to transiently transition between epithelial and mesenchymal states is critical to complete the metastatic process. In contrast, induction of epithelial-mesenchymal transition (EMT) through the acquisition of drug persistence is a more stable event. Herein, we utilize Her2 transformed human mammary epithelial (HMLE) cells to compare a reversible model of EMT induced by TGF-beta to a stable mesenchymal phenotype induced by chronic exposure to the ErbB kinase inhibitor, lapatinib. Indeed, only a TGF-beta cells capable of returning to an epithelial phenotype resulted in long bone metastasis (BM). These four cell populations were anylzed by RNA sequencing.
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Project description:Epithelial-mesenchymal transition (EMT), a switch of polarized epithelial cells to a migratory, fibroblastoid phenotype, is considered a key process driving tumor cell invasiveness and metastasis. Using breast cancer cell lines as a model system, we sought to discover gene-expression signatures of EMT with clinical and mechanistic relevance. A supervised comparison of epithelial and mesenchymal breast cancer lines defined a 200-gene EMT signature that was prognostic across multiple breast cancer cohorts. Immunostaining of LYN, a top-ranked EMT signature gene and Src-family tyrosine kinase, was associated with significantly shorter overall survival (P=0.02), and correlated with the basal-like (“triple-negative”) phenotype. In mesenchymal breast cancer lines, RNAi-mediated knockdown of LYN inhibited cell migration and invasion, but not proliferation. Dasatinib, a dual-specificity tyrosine kinase inhibitor, also blocked invasion (but not proliferation) at nanomolar concentrations that inhibit LYN kinase activity, suggesting that LYN is a likely target and invasion a relevant endpoint for dasatinib therapy. Our findings define a prognostically-relevant EMT signature in breast cancer, and identify LYN as a mediator of invasion and possible new therapeutic target (and theranostic marker for dasatinib response), with particular relevance to clinically-aggressive basal-like breast cancer. Cell Line: cell line(epithelial-like/fibroblast-like/normal breast fibroblasts) Keywords: Logical Set Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. HEEBO oligonucleotide microarrays from the Stanford Functional Genomics Facility were used to perform gene expression profiling of 20 human breast cell lines, in comparison to a universal RNA reference. Expression data were analyzed by Significance Analysis of Microarrays to identify a 200-gene signature characteristic of EMT.
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