Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJDB14279 | ENA |
REPOSITORIES: ENA
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Project description:Overexpression of the Polycomb group protein Enhancer of Zeste Homolog 2 (EZH2) occurs in diverse malignancies, including prostate cancer, breast cancer, and glioblastoma multiforme (GBM) (1). Based on its ability to modulate transcription of key genes implicated in cell cycle control, DNA repair and cell differentiation, EZH2 is believed to play a crucial role in tissue-specific stem cell maintenance and tumor development. Here we show that targeted pharmacologic disruption of EZH2 by the S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin A (DZNep), or its specific down-regulation by shRNA, strongly impairs GBM cancer stem cell self-renewal in vitro and tumor-initiating capacity in vivo. Using genome-wide expression analysis of DZNep-treated GBM cancer stem cells, we found the expression of c-myc, recently reported to be essential for GBM cancer stem cells, to be strongly repressed upon EZH2 depletion. Specific shRNA-mediated down-regulation of EZH2 in combination with chromatin immunoprecipitation (ChIP) experiments revealed that c-myc is a direct target of EZH2 in GBM cancer stem cells. Taken together, our observations provide evidence that direct transcriptional regulation of c-myc by EZH2 may constitute a novel mechanism underlying GBM cancer stem cell maintenance and suggest that EZH2 may be a valuable new therapeutic target for GBM management. Experiment Overall Design: Three samples of cancer stem-cell enriched gliospheres from primary glioblastoma multiforme cell cultures were treated with DZNep. Untreated gliospheres from the same cultures were used as controls.
2009-12-14 | E-GEOD-18150 | biostudies-arrayexpress
Project description:Expression data from breast cancer tumor-initiating cells
| PRJNA147827 | ENA
Project description:Overexpression of the Polycomb group protein Enhancer of Zeste Homolog 2 (EZH2) occurs in diverse malignancies, including prostate cancer, breast cancer, and glioblastoma multiforme (GBM) (1). Based on its ability to modulate transcription of key genes implicated in cell cycle control, DNA repair and cell differentiation, EZH2 is believed to play a crucial role in tissue-specific stem cell maintenance and tumor development. Here we show that targeted pharmacologic disruption of EZH2 by the S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin A (DZNep), or its specific down-regulation by shRNA, strongly impairs GBM cancer stem cell self-renewal in vitro and tumor-initiating capacity in vivo. Using genome-wide expression analysis of DZNep-treated GBM cancer stem cells, we found the expression of c-myc, recently reported to be essential for GBM cancer stem cells, to be strongly repressed upon EZH2 depletion. Specific shRNA-mediated down-regulation of EZH2 in combination with chromatin immunoprecipitation (ChIP) experiments revealed that c-myc is a direct target of EZH2 in GBM cancer stem cells. Taken together, our observations provide evidence that direct transcriptional regulation of c-myc by EZH2 may constitute a novel mechanism underlying GBM cancer stem cell maintenance and suggest that EZH2 may be a valuable new therapeutic target for GBM management.
2009-11-30 | GSE18150 | GEO
Project description:The CD44hi compartment in human breast cancer is enriched in tumor-initiating cells, however the functional heterogeneity within this subpopulation remains poorly defined. From a human breast cancer cell line with a known bi-lineage phenotype we have isolated and cloned two CD44hi populations that exhibited mesenchymal/Basal B and luminal/Basal A features, respectively. Rather than CD44+/CD24-,Basal B (G4) cells, only CD44hi/CD24lo, epithelioid Basal A (A4) cells retained a tumor-initiating capacity in NOG mice, form mammospheres and exhibit resistance to standard chemotherapy. Microarray data obtained from Affymetrix Human Gene 1.0 ST Array Five replicates of A4 and 5 replicates of G4
2012-06-11 | E-GEOD-32455 | biostudies-arrayexpress
Project description:The gene expression of two different tumorigenic human breast epithelial cell types (HMLER and BPLER) is compared with their immortalized parental cell-of-origin (HME and BPE). Keywords: breast cancer, cell-of-origin, HMEC, BPEC,metastasis, tumor stem cells, tumor initiating cells, breast adenocarcinoma
2007-08-15 | GSE6885 | GEO
Project description:Glioma initiating cells/stem cells exist in the bulk tumor of glioblastoma. This cell population contributes to the frequent resistances toward radiation/chemotherapy, aggressiveness of adult brain cancer and increased recurrence rate. Targeting stem cell
2018-02-23 | GSE92458 | GEO
Project description:Targetable genes-associated tumor-initiating program in breast cancer
| PRJNA374893 | ENA
Project description:Cancer stem-like cells (CSCs) are thought to be responsible for recurrence of tumors and poor prognosis because of their higher tumor initiating ability and drug resistance, though the mechanisms remain still unclear. Here, we show a critical role of mini-chromosome maintenance protein (MCM) 10, a component of DNA replication machinery, in enabling CSCs to deal with DNA replicative stress. Our transcriptomic analysis of patient-derived cultured breast cancer cells revealed that MCM10 is strongly upregulated in CSC-enriched spheroid cells, compared to cancer cells cultured in a regular condition. Elevated MCM10 expression was correlated with worse prognosis of patients with breast cancer. Depletion of MCM10 resulted in not only reduced cell proliferation and tumorigenesis, but also reduced tumor sphere forming efficiency, expression levels of stemness markers, and the tumor initiating ability. These results indicate that MCM10 is essential for maintenance of CSCs as well as for tumor cell proliferation. DNA fiber assay revealed that CSCs have a comparatively high level of DNA replicative stress. Overexpression of MCM10 helped cells to proliferate in a medium containing hydroxyurea (HU), a replicative stress-inducing chemotherapeutic agent. Conversely, MCM10 depletion made cells more fragile to replicative stress induced by HU or mitomycin C (MMC), another replicative stress inducer. Therefore, MCM10 plays critical roles for dealing with the enhanced replicative stress generated in CSCs for their survival, leading to maintenance of tumor initiating ability and drug resistance. We provide a preclinical rationale to target MCM10, the critical mediator for DNA replicative stress, for breast cancer that includes CSCs.
2021-09-09 | GSE127264 | GEO
Project description:The Epithelial-to-Mesenchymal Transition (EMT) is a dynamic cellular program that is frequently used by cancer cells to increase migratory and invasive cell characteristics. It is a key contributor to both heterogeneity and chemo-resistance and metastasis in many solid tumors, including triple negative breast cancer. In particular, the intermediate or hybrid EMT state has increased tumor initiating and stem-like properties. Here, we have identified multiple distinct EMT states derived from the human breast cell line, SUM149PT, including three unique intermediate states, possessing distinct migratory, tumor initiating, and metastatic qualities. We have used this model to interrogate the epigenetic landscape of these distinct EMT states in a multi-omics approach, identifying and RUNX2 as relevant in regulating the intermediate state, as well as to develop a novel multiplexed staining approach to evaluate E-M heterogeneity (EMH) and overall EMT score in orthotopic tumors as well as patient tumor samples. This model reveals insights into the complex EMT spectrum of cell states, the networks that control them, and how EMT plasticity contributes to tumor heterogeneity in breast cancer.
2022-02-15 | GSE172609 | GEO
Project description:The Epithelial-to-Mesenchymal Transition (EMT) is a dynamic cellular program that is frequently used by cancer cells to increase migratory and invasive cell characteristics. It is a key contributor to both heterogeneity and chemo-resistance and metastasis in many solid tumors, including triple negative breast cancer. In particular, the intermediate or hybrid EMT state has increased tumor initiating and stem-like properties. Here, we have identified multiple distinct EMT states derived from the human breast cell line, SUM149PT, including three unique intermediate states, possessing distinct migratory, tumor initiating, and metastatic qualities. We have used this model to interrogate the epigenetic landscape of these distinct EMT states in a multi-omics approach, identifying and RUNX2 as relevant in regulating the intermediate state, as well as to develop a novel multiplexed staining approach to evaluate E-M heterogeneity (EMH) and overall EMT score in orthotopic tumors as well as patient tumor samples. This model reveals insights into the complex EMT spectrum of cell states, the networks that control them, and how EMT plasticity contributes to tumor heterogeneity in breast cancer.
2022-02-15 | GSE172608 | GEO