|
|
GEO help: Mouse over screen elements for information. |
|
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)
|
|
Relations |
BioProject |
PRJNA574449 |
Supplementary file |
Size |
Download |
File type/resource |
GSE138072_RAW.tar |
448.7 Mb |
(http)(custom) |
TAR (of IDAT) |
Processed data included within Sample table |
|
|
|
|
|