Similar Datasets
Project description:Background: The well-characterized function of the transcriptional repressor, Slug, is to promote EMT and tumor invasion/metastasis by down-regulating E-cadherin expression. In this study, we investigated the significance of Slug during the S phase. Method: Slug mRNA expression was isolated from thymidine-arrested CL1-5/AS2neo (control) and CL1-5/AS2neo-Slug-WT stable cells. The Agilent oligonucleotide microarray analysis was performed to identify Slug downstream genes. Results: Overexpression of Slug inhibited lung [3H]-thymidine incorporation and delayed S phase progression. By using Agilent microarray we have identified panel of genes altered by Slug overexpression. Slug can down-regulate target genes about cell cycle networks for DNA replication, DNA replication checkpoint and genomic stability, such as TOP1, ORC4, RFC3, and Rad17. Conclusions: the multifaceted role of Slug in cancer progression by controlling the epithelial-mesenchymal transition and genome stability. Two-condition experiment, Vector vs. Slug overexpression cells. The cDNAs encoding full-length human Slug were amplified and subcloned into lentiviral pLKO_AS2.neo which generated full-length Slug. Vector control or Slug lentivirus were transduced into CL1-5 cells and Gentamycin was used to select stable cells.
2012-02-09 | E-GEOD-35617 | biostudies-arrayexpress
Project description:Background: The well-characterized function of the transcriptional repressor, Slug, is to promote EMT and tumor invasion/metastasis by down-regulating E-cadherin expression. In this study, we investigated the significance of Slug during the S phase. Method: Slug mRNA expression was isolated from thymidine-arrested CL1-5/AS2neo (control) and CL1-5/AS2neo-Slug-WT stable cells. The Agilent oligonucleotide microarray analysis was performed to identify Slug downstream genes. Results: Overexpression of Slug inhibited lung [3H]-thymidine incorporation and delayed S phase progression. By using Agilent microarray we have identified panel of genes altered by Slug overexpression. Slug can down-regulate target genes about cell cycle networks for DNA replication, DNA replication checkpoint and genomic stability, such as TOP1, ORC4, RFC3, and Rad17. Conclusions: the multifaceted role of Slug in cancer progression by controlling the epithelial-mesenchymal transition and genome stability.
2012-02-09 | GSE35617 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE41026: Expression analysis of HepG2, HepG2-slug and HepG2-slug on Matrigel GSE41027: Chip-chip from HepG2 cells and HepG2 cells with slug overexpression Refer to individual Series
2012-09-21 | E-GEOD-41028 | biostudies-arrayexpress
Project description:Gene expression profiling of MDCK epithelial cells expressing different repressors (MDCK-Snail, MDCK-Slug and MDCK-E47 cells) versus control MDCK cells. Keywords: Genetic Modification (overexpression of E-cadherin repressors)
2006-11-02 | GSE4151 | GEO
Project description:Neoadjuvant chemotherapy (NACT) followed by radical surgery for patients in FIGO stages IB2-IIB has proven to reduce tumor volume and numbers. However, NACT followed by radical surgery has not been found to improve overall survival. In this study, 35 paired pre/post-NACT cervical cancer tissues and 167 cervical cancer samples were examined by immunohistochemical analysis, SLUG expression was potentially increased in cervical cancer tissues after neoadjuvant chemotherapy, which in turn positively correlated with pelvic lymph node metastasis. The expression of SLUG following neoadjuvant chemotherapy was identified as a poor survival indicator. Functional assays, Agilent microarray hybridization and CHIP assay were performed to determine SLUG’s downstream genes and pathways. SLUG overexpression promoted metastasis in cervical cancer in both in vitro and in vivo models, whereas SLUG silencing had the opposite effect. Mechanically, SLUG is not a prerequisite for EMT activation in cervical cancer models, but contributes to the invasiveness and metastasis of cervical cancer cells by directly tethering to the recognition sequence GCCAGGTGC in the MMP3 promoter region. Our results provide mechanistic insight into the potential pro-cancer effect of neoadjuvant chemotherapy, and demonstrates that the SLUG-MMP3 axis could serve as a target for improving the efficacy of chemotherapy.
2020-12-11 | GSE163002 | GEO
Project description:The epithelial-mesenchymal transition (EMT) regulator Slug has multifaceted roles in controlling lung cancer progression, but the downstream targets and underlying mechanisms of Slug remain undetermined. The miRNAs downstream of Slug in lung cancer cells were examined using Illumina bead arrays and TaqMan low-density arrays.
2017-01-01 | GSE84040 | GEO
Project description:Cancer stem cells (CSCs) are proposed to be responsible for metastatic dissemination and clinical relapse in a variety of cancers. Analogies between CSCs and normal tissue stem cells (SC) has led to the notion that CSCs often co-opt the normal SC program of their tissue-of-origin. The cell-biological program termed epithelial-mesenchymal transition (EMT) has been found to encourage entrance of normal and neoplastic mammary cells into the corresponding SC states. Using genetically engineered knock-in reporter mouse lines, we demonstrate that in the murine mammary lineage, the paralogous EMT-inducing transcription factors Snail and Slug, are selectively exploited by CSCs and normal SCs respectively. Slug, when expressed at physiological levels, only activates a partial EMT program and is dispensable in CSCs. In contrast, Snail drives a far more complete transition into the mesenchymal state and controls both tumor-initiation and metastatic dissemination. Consistent with their functional distinctions, Snail controls far more target genes than Slug, and their distinct functions are determined by their divergent N-terminal domains. Our findings underscore fundamental distinctions between the SC program operating in normal and neoplastic SCs, and hint for potential avenues of selective therapeutic elimination of breast CSCs. We sought to understand differential ability to activate the EMT program in breast cancer cells by transcription factors Snail and Slug. Hence, we mapped genome-wide Snail and Slug binding sites in murine MMTV-PyMT breast cancer cell lines that express high level of Snail or high level of Slug respectively. Specifically, we performed Snail ChIP seq in the mesenchymal pBl.3G cells, and Slug ChIP-seq in the epithelial pBl.1G cells.
2015-09-02 | E-GEOD-61198 | biostudies-arrayexpress
Project description:The transcription factor slug represses genes with E-box and then activates cancer stem cell related pathway: Wnt, Notch and Hedgehog pathway. Chromatin immunoprecipitation (ChIP) of slug by ChIP-on-chip analysis demonstrated that slug indirectly activates cancer stem cell related pathway and thus promotes vasculogenic mimicry formation.
2012-09-21 | GSE41027 | GEO
Project description:Purpose: The acquisition of cellular invasiveness of breast epithelial cells and subsequent transition from ductal carcinoma in situ (DCIS) to invasive breast cancer is a critical step in breast cancer progression. Very little is known about the molecular dynamics governing this transition. We have previously shown that overexpression of the transcriptional regulator TBX3 in DCIS-like 21NT cells results in increased survival, growth, and invasiveness. In this study we explore the role of TBX3 in breast cancer progression pathways, focusing specifically on its involvement in the induction of EMT and the transition from DCIS to invasive mammary carcinoma. Methods: Total mRNA was isolated from 21NT transfected cell lines. Sequencing was conducted using an Illumina HiSeq 2500 sequencer, comparing the resultant transcriptional profiles with overexpression of either TBX3 isoform (TBX3iso1 or TBX3iso2) as fold changes relative to the empty vector control. RNA-Seq data was integrated with ChIP-array data downstream to assess direct targets of TBX3 isoforms and relate it to the process of EMT. TBX3, SLUG and TWIST1 expression were assessed by immunohistochemistry in two independent early-stage (Stage 0 and Stage 1) breast cancer cohorts. Results: An EMT-related transcriptional profile was observed with overexpression of TBX3iso1 and TBX3iso2. Using genome-wide bioinformatic approaches in conjunction with more conventional in vitro studies, we have identified SLUG and TWIST1 as downstream targets of TBX3 and have assessed their expression by immunohistochemistry in two different patient cohorts. Our findings suggest that TBX3 facilitates the process of early invasion in DCIS lesions by promoting the induction of EMT and tumor progression through the low-grade pathway. Finally, we propose a progression model in which SLUG is an important and necessary effector downstream of TBX3, leading to increased motility, invasiveness, and induction of key invasiveness-associated genes. Conclusions: This is the only existing study which has conducted assessment of transcriptional changes associated with TBX3 isoforms (TBX3iso1 and TBX3iso2). Our published study has identified the transcriptional regulator TBX3 as an enabler of EMT in non-high grade, pre-invasive lesions of the breast, inducing SLUG and promoting the transition from in situ (DCIS) to invasive breast cancer.
2019-02-07 | GSE126154 | GEO
Project description:Purpose:To identify transcriptional changes in human endothelial cells (HUVEC) both during normal sprouting angiogenesis (different time points) and with Slug overexpression (different Slug expression), in a 3D fibrin-gel bead angiogenesis Methods: Angiogenic endothelial cell with different level of Slug expression (normal and overexpressing) at different stage (early/sprouting and late/lumen formation) were harvested from a 3D fibrin-gel bead angiogenesis assay. Their transcriptom profile was generated by Next Generation RNA-sequencing as single reads, performed on an Illumina HiSeq 2500 platform, using three donor HUVEC lines.At least 30 million reads per sample were sequenced. Quality control was performed on data using FASTQC(v. 0.11.2), and reads were trimmed using Trimmomatic(v.0.32) with Illumina TruSeq adapter sequences using a PHRED quality score 15 and minimum length 20 bases. Trimmed reads were then aligned to the human hg19 reference genome using the Ensembl GRCh37 annotations and post processed using Tophat2(v.2.0.12), Bowtie2(v.2.2.3) and Samtools(v.0.1.19). Expression levels were quantified both with FPKM (Fragment per kilobase per million mapped reads) using Cufflinks(v. 2.1.1) and with raw counts using HTSeq(v.0.6.1p1.). Differential analysis was done using DESeq2 and significant genes were considered (p-value < 0.05, 2 fold change). K-means clustering was performed to extract dynamic gene clusters based on differential expression between GFP and SLUG knockdown time-points. Gene set enrichment analysis (GSEA) was performed on expressed genes to identify significant gene sets across sample comparisons. Additional gene ontology analysis was performed for each cluster and reported using Metascape. Clustering was performed in R and heatmaps were generated using JavaTree. Results: Using several different gene expression analysis platforms, we found consistent and significant changes, during both normal angiogenesis and with Slug overexpression, in genes related to proliferation, migraion, cell morphology/polarity and junction regulations, all of which are consistent with a partial-EMT program. We also found changes in Notch signaling components in Slug overexpressing cells. Changes in specific genes related to EMT and Notch signaling were validated with both qPCR and WB. Conclusion: This is the first comprehensive transcriptome analysis in human angiogenic EC during normal and excessive sprouting induced by Slug expression in an in vitro 3D angiogenesis assay system. We conclude that a partial-EndoMT is necessary for normal angiogenesis and that endothelial Slug expresion level regulates Notch signaling to determines at least partly the extent of EC's commitment towards a mesenchymal identity.
2020-08-01 | GSE154546 | GEO