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Series GSE138072 Query DataSets for GSE138072
Status Public on Dec 22, 2020
Title Epigenetic rewiring towards mesenchymal-epithelial transformation in ovarian cancer-associated mesenchymal stem cells drives metastasis
Organism Homo sapiens
Experiment type Methylation profiling by array
Summary Ovarian cancer develops early intra-peritoneal metastasis establishing a pro-tumorigenic tumor microenvironment (TME) through reprogramming normal mesenchymal stem cells into carcinoma-associated mesenchymal stem cells (CA-MSCs). CA-MSCs are the stromal stem cell of the TME, supporting cancer growth, increasing desmoplasia, angiogenesis and chemotherapy resistance. We demonstrate epigenetic rewiring drives CA-MSC formation via enhancer-enriched DNA hypermethylation, altered chromatin accessibility and differential histone modifications inducing a partial mesenchymal to epithelial transition (MET) increasing tumor cell adhesion. Direct CA-MSC:tumor cell interactions, confirmed in patient ascites, facilitate ovarian cancer metastasis through co-migration. WT1, a developmental mediator of MET, and EZH2, mediate CA-MSC epigenetic reprogramming. WT1 overexpression induces CA-MSC conversion while WT1 knock-down, in combination with EZH2 inhibition, blocks CA-MSC formation. EZH2 inhibition subsequently decreases intra-abdominal metastasis.
 
Overall design 13 cancer-associated mesenchymal stem cell, and 19 normal mesenchymal stem cell samples are profiled.
 
Contributor(s) Hui S, Lan C
Citation(s) 33296650
Submission date Sep 26, 2019
Last update date Dec 22, 2020
Contact name Hui Shen
E-mail(s) Hui.Shen@vai.org
Organization name Van Andel Research Institute
Department Center for Epigenetics
Lab Shen Lab
Street address 333 Bostwick Ave NE
City Grand Rapids
State/province MI
ZIP/Postal code 49503
Country USA
 
Platforms (1)
GPL23976 Illumina Infinium HumanMethylation850 BeadChip
Samples (32)
GSM4097954 CAMSC_OM01
GSM4097955 CAMSC_OM02
GSM4097956 CAMSC_OM03a
Relations
BioProject PRJNA574449

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE138072_RAW.tar 448.7 Mb (http)(custom) TAR (of IDAT)
Processed data included within Sample table

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