Expression data from MTDH knockdown in the Hec50co endometrial cancer cell line
Transcriptomics Dataset
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General Information
AccessionGSE26134
TitleExpression data from MTDH knockdown in the Hec50co endometrial cancer cell line
DescriptionUnderstanding the molecular underpinnings of chemoresistance is vital to design therapies to restore chemosensitivity. In particular, metadherin (MTDH) has been demonstrated to have a critical role in chemoresistance. Over-expression of MTDH has recently been implicated in poor clinical outcome in breast cancer, neroblastoma, hepatocellular carcinoma and prostate cancer. In this present study, we focused on the therapeutic benefit of MTDH depletion to restore sensitivity to cell death mediated by a combinatorial therapy of tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL), which promotes death of cancerous cells of the human reproductive tract, and histone deacetylase (HDAC) inhibitors, which have been shown to increase sensitivity of cancer cells to TRAIL-induced apoptosis. Our data indicate that depletion of MTDH in endometrial cancer cells results in sensitization of cells that were previously resistant to cell death mediated by combinatorial treatment with TRAIL and HDAC inhibitor LBH589. MTDH was found to be involved in G2/M checkpoint regulation in response to LBH589 alone or LBH589 in combination with TRAIL, suggesting that MTDH functions at the cell cycle checkpoint to accomplish resistance.Using microarray technology, we identified 57 downstream target genes of MTDH, including Calbindin 1 and Galectin 1, which may contribute to MTDH-mediated resistance to combinatorial TRAIL and HDAC inhibitor targeted therapy. Inhibition of PDK1,AKT phosphorylation and increase Bim expression and XIAP degradation may result in sensitivity to cell death induction in MTDH depleted Hec50co cells by TRAIL and LBH 589 combination treatment. These findings indicate that depletion of MTDH is a potentially novel avenue for effective cancer therapy.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE26134
RepositoryGene Expression Omnibus
Tools used to analyze the dataset
Keyword
Dataset Accession
Enrichr
Published May 2016
A comprehensive gene set enrichment analysis web server 2016 update
7759
65
Characteristic Direction
Published March 2014
A geometrical multivariate approach to identify differentially expressed genes
26829
GeneMANIA
Published June 2010
Biological network integration for gene prioritization and predicting gene function
7435
L1000CDS2
Published August 2016
An ultra-fast LINCS L1000 Characteristic Direction signature search engine
7756
PAEA
Published November 2015
Enrichment analysis tool implementing the principal angle method
3879
Canned Analyses generated with the dataset
Filters  
Dataset Accession
Tool Name
Direction
Geneset
Small molecules which mimic MTDH KD
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse MTDH KD
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which rev...
Enrichment analysis of genes dysregulated in MTDH KD
PAEA, Characteristic Direction
An enrichment analysis was performed on the top most dyresgulated genes determined by appl...
Interaction network and enrichment analysis of genes downregulated in MTDH KD
GeneMANIA, Characteristic Direction
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Interaction network and enrichment analysis of genes upregulated in MTDH KD
GeneMANIA, Characteristic Direction
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Enrichment analysis of genes downregulated in MTDH KD
Enrichr, Characteristic Direction
An enrichment analysis was performed on the top 500 most downregulated genes identified by...
Enrichment analysis of genes upregulated in MTDH KD
Enrichr, Characteristic Direction
An enrichment analysis was performed on the top 500 most upregulated genes identified by a...
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