Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA153615 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Efforts to improve the clinical outcome of highly aggressive triple-negative breast cancer (TNBC) have been hindered by the lack of effective targeted therapies. Thus, it is important to identify the specific gene targets/pathways driving the invasive phenotype to develop more effective therapeutics. Here we show that ubiquitin-associated and SH3 domain-containing B (UBASH3B), a protein tyrosine phosphatase, is overexpressed in TNBC, where it supports malignant growth, invasion, and metastasis largely through modulating epidermal growth factor receptor (EGFR). We also show that UBASH3B is a functional target of anti-invasive microRNA200a (miR200a) that is down-regulated in TNBC. Importantly, the oncogenic potential of UBASH3B is dependent on its tyrosine phosphatase activity, which targets CBL ubiquitin ligase for dephosphorylation and inactivation, leading to EGFR up-regulation. Thus, UBASH3B may function as a crucial node in bridging multiple invasion-promoting pathways, thereby providing a potential therapeutic target for TNBC.
2013-06-01 | GSE36693 | GEO
Project description:Efforts to improve the clinical outcome of highly aggressive triplenegative breast cancer (TNBC) have been hindered by the lack of effective targeted therapies. Hence, it is important to identify the specific gene targets/pathways driving the invasive phenotype to develop more effective therapeutics. Here we show that UBASH3B (ubiquitin associated and SH3 domain containing B), a protein tyrosine phosphatase, is overexpressed in TNBC, where it supports malignant growth, invasion and metastasis in large through modulating EGFR. We also show that UBASH3B is a functional target of anti-invasive miR-200a that is downregulated in TNBC. Importantly, the oncogenic potential of UBASH3B is dependent on its tyrosine phosphatase activity, which targets CBL ubiquitin ligase for dephosphorylation and inactivation, leading to EGFR upregulation. Thus, UBASH3B may function as a crucial node in bridging multiple invasion-promoting pathways, thus providing a potential new therapeutic target for TNBC. Breast cancer tissues and breast cancer cell lines
2013-06-01 | E-GEOD-36693 | biostudies-arrayexpress
Project description:Triple-negative breast cancer is a highly aggressive tumor subtype that lacks effective therapeutic targets. Here, we show that ELK3 is overexpressed in a subset of breast cancers, in particular basal-like and normal-like/claudin-low cell lines. Suppression of ELK3 in MDA-MB-231 cells led to transdifferentiation from an invasive mesenchymal phenotype to a non-invasive epithelial phenotype both in vitro and in vivo. Suppression of ELK3 results in the extensive changes in genome expression profiles. Among these, GATA3, a master suppressor of metastasis, was epigenetically activated and we found that suppression of GATA3 led to the restoration of migration and invasion. These results suggest that the ELK3-GATA3 axis is a major pathway that promotes metastasis of MDA-MB-231 cells. Retrovirus expressing shRNA of ELK3 was transduced into MDA-MB-231 cell line and stable cell line of which ELK3 is suppressed more than 50% was selected by the drug selection (Puromycin).
2016-06-15 | E-GEOD-83325 | biostudies-arrayexpress
Project description:Triple-negative breast cancer is a highly aggressive tumor subtype that lacks effective therapeutic targets. Here, we show that ELK3 is overexpressed in a subset of breast cancers, in particular basal-like and normal-like/claudin-low cell lines. Suppression of ELK3 in MDA-MB-231 cells led to transdifferentiation from an invasive mesenchymal phenotype to a non-invasive epithelial phenotype both in vitro and in vivo. Suppression of ELK3 results in the extensive changes in genome expression profiles. Among these, GATA3, a master suppressor of metastasis, was epigenetically activated and we found that suppression of GATA3 led to the restoration of migration and invasion. These results suggest that the ELK3-GATA3 axis is a major pathway that promotes metastasis of MDA-MB-231 cells.
2016-06-15 | GSE83325 | GEO
Project description:Purpose: The BET family protein BRD4 is an important anti-tumor target and is highly expressed in breast cancer. However, BET inhibitors are susceptible to drug resistance. The aim of this study is to explore the mechanism of BET inhibitor JQ-1 combined with cardamonin in the anti-invasion and metastasis of triple-negative breast cancer. Methods: triple-negative breast cancer cells mRNA of DMSO (Control), JQ-1,cardamonin and combined groups were progressed with deep sequencing, in triplicate through Illumina sequencing platform (HiSeqTM 2500). Genes with adjusted P-value < 0.01 and |foldChange| > 2 were defined as differentially expressed genes (DEGs) and subjected to the following GO and KEGG enrichment. qRT-PCR was performed to validate several essential genes using QuantStudio 5 (Thermo Fisher) and SYBR Green assays. Results: As an inhibitor of mTOR, Cardamonin(CAR) can inhibit the proliferation of tumors. Research have found that BET inhibitor can affect the function of a large number of genes by regulating the epigenome, which plays an important role in a variety of diseases. In this study we explored the JQ1 which is a BRD4 protein inhibitor can inhibit the proliferation and metastasis of MDA-MB-231 cells in triple-negative breast cancer cell lines, and this phenomenon can be significantly enhanced when CAR is combined with JQ-1, and the same results are shown in mouse tumor formation experiments and triple-negative breast cancer organoids. At the same time, RNA-seq was performed in MD1-MB-231 cells to explore the changes of specific molecular signaling pathways. We have mapped over 40 million sequence reads to the MDA-MB-231 cell line genome in each specimen.Compared with the control group, CAR and JQ1, the combination group has significantly enriched gene expression. KEGG and GO enrichment analysis indicate that the combination group showed a series of biological processes such as macroautophagy, negative regulation of cell growth, lipid catabolic process, which led to decreased cell viability and decreased proliferation and metastasis ability. Conclusions: In this study, we demonstrated that JQ-1 combined with cardamomin could inhibit the invasion and metastasis of triple-negative breast cancer MDA-MB-231 cells, induce cell cycle arrest and promote cell apoptosis. The results of RNA-Seq were consistent with our in vitro and in vivo experiments, which demonstrated that the combination of JQ-1 and cardamonin effectively inhibited the proliferation, invasion and metastasis of MDA-MB-231 cells.
2024-01-01 | GSE236250 | GEO
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
2010-04-11 | GSE13915 | GEO
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.
2010-04-11 | E-GEOD-13915 | biostudies-arrayexpress
Project description:Triple-Negative Breast Cancer (TNBC) is a poorly targetable cancer subtype that exhibits a high metastatic potential. To develop new intervention strategies, it is crucial to understand the mechanisms governing migratory and invasive features of TNBC cells. Previously it was shown that high expression of the non-receptor tyrosine kinase FER is an independent prognostic factor that correlates with poor survival in high grade and basal breast cancer. Here, we show that FER controls proliferation and invasion of TNBC cells through the direct substrates MAPK1 and Dynactin 2 (DCTN2; Dynamitin). Our data demonstrate that FER regulates tumor cell proliferation through phosphorylation of MAPK1 on tyrosine 187, and recycling endosome function and subsequent invasion of breast cancer cells through tyrosine 6 residue (Y6) of DCTN2. We show that DCTN2-Y6 is essential for Dynein complex formation and the development of tubular recycling domains at the early endosome. By controlling this crucial step in endosomal recycling, FER drives and sustains adhesion and invasion of (triple negative) breast cancer cells. Our data provide clinical ramification by demonstrating that high grade and basal breast cancers expressing elevated FER levels are more susceptible to taxane-based chemotherapy interventions. In conclusion, our study links FER to kinase-dependent control of intracellular vesicular transport and tumor progression in breast cancer. Importantly, our results indicate that FER represents a predictive and functional biomarker in high grade basal breast cancers.
2022-04-15 | PXD021307 | Pride
Project description:This SuperSeries is composed of the following subset Series: GSE21719: Identification of the receptor tyrosine kinase AXL in triple negative breast cancer as a novel target for the human miR-34a microRNA (miRNA study) GSE21832: Identification of the receptor tyrosine kinase AXL in triple negative breast cancer as a novel target for the human miR-34a microRNA (gene expression) Refer to individual Series
2010-12-31 | E-GEOD-21834 | biostudies-arrayexpress
Project description:Metastasis in triple-negative breast cancer
| PRJNA437929 | ENA