 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Nov 18, 2022 |
| Title |
Epigenetic regulator Smarcd3 is required for established tumor growth in pancreatic cancer |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Pancreatic ductal adenocarcinoma (PDAC) is a disease characterized by aggressive metastasis and resistance to therapy, making clinical management a significant challenge. As cancer progresses, developmental signals are often aberrantly re-activated, driving the self-renewal of cancer cells and malignant features of disease. Given the central role for epigenetic regulation in development, we hypothesized that epigenetic factors may be required to sustain the self-renewal of pancreatic cancer cells. Here, we used a functional screen to identify Smarcd3, a component of the SWI/SNF (BAF) nucleosome remodeling complex, as a novel functional dependency in PDAC. SWI/SNF coordinates context-specific gene regulation in development and is frequently dysregulated in cancer. However, Smarcd3 has not been linked to functions in PDAC and represents a new epigenetic mediator of cancer function. We found that Smarcd3 was uniquely up-regulated in PDAC stem cells and was required for the in vivo propagation of mouse and patient-derived tumors. Furthermore, using integrated RNA-seq, ChIP-seq, and network analysis we showed that Smarcd3 regulates global SWI/SNF binding and histone acetylation, driving the epigenetic regulation of lipid metabolic programs. Specifically, we found that Smarcd3 regulated genes converging on fatty acid metabolism, which has been directly implicated in stem signaling in PDAC. Collectively, these data identify Smarcd3 as a critical novel dependency and epigenetic regulator of lipid metabolism pancreatic cancer.
|
| |
|
| Overall design |
ChIP-seq for Smarca4, Arid1a, H3K4me, H3K4me3 and H3K27ac in KPf/fC cells transduced with shControl or shSmarcd3; RNA-seq in KPf/fC cells transduced with shControl or shSmarcd3.
|
| |
|
| Contributor(s) |
Gatchalian J, Ferguson LP, Hargreaves D, Reya T |
| Citation(s) |
36653361 |
| |
| Submission date |
Mar 08, 2021 |
| Last update date |
Feb 06, 2023 |
| Contact name |
Diana C. Hargreaves |
| E-mail(s) |
dhargreaves@salk.edu
|
| Organization name |
The Salk Institute for Biological Studies
|
| Street address |
10010 North Torrey Pines Road
|
| City |
San Diego |
| State/province |
CA |
| ZIP/Postal code |
92037 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (29)
|
|
| Relations |
| BioProject |
PRJNA707552 |
| SRA |
SRP309820 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE168490_RAW.tar |
2.4 Gb |
(http)(custom) |
TAR (of BEDGRAPH) |
| GSE168490_getDiffExp_Output_KPC_shControl_shSmarcd3.txt.gz |
1.9 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...