GEO series
Metastatic site influences driver gene function in pancreatic cancer [ATAC-seq]
GSE245821
Mus musculus
Genome binding/occupancy profiling by high throughput sequencing
16 samples
Submitted 2025/05/14
Platform GPL21103
Summary
Driver gene mutations can increase the metastatic potential of the primary tumor, but their role in sustaining tumor growth at metastatic sites is poorly understood. A paradigm of such mutations is inactivation of SMAD4 – a transcriptional effector of TGFβ signaling – which is a hallmark of multiple gastrointestinal malignancies. SMAD4 inactivation mediates TGFβ’s remarkable anti- to pro-tumorigenic switch during cancer progression and can thus influence both tumor initiation and metastasis. To determine whether metastatic tumors remain dependent on SMAD4 inactivation, we developed a mouse model of pancreatic ductal adenocarcinoma (PDAC) that enables Smad4 depletion in the pre-malignant pancreas and subsequent Smad4 reactivation in established metastases. As expected, Smad4 inactivation facilitated the formation of primary tumors that eventually colonized the liver and lungs. By contrast, Smad4 reactivation in metastatic disease had opposite effects depending on the tumor’s organ of residence: suppression of liver metastases and promotion of lung metastases. Integrative multiomic analysis revealed organ-specific differences in the tumor cells’ epigenomic state, whereby the liver and lungs harbored chromatin programs respectively dominated by the KLF and RUNX developmental transcription factors, with Klf4 depletion being sufficient to reverse Smad4’s tumor-suppressive activity in liver metastases. Our results show how epigenetic states favored by the organ of residence can influence the function of driver genes in metastatic tumors. This organ-specific gene–chromatin interplay invites consideration of anatomical site in the interpretation of tumor genetics, with implications for the therapeutic targeting of metastatic disease.
Published in
Tsanov KM, Barriga FM, Ho YJ et al.
· Nature cancer 2025
· PMID 40999053
· doi:10.1038/s43018-025-01047-5
This dataset
Download
Direct links to NCBI, no account and no request form: the whole study as GSE245821_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 16 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1030029 and SRA study SRP467418. Searching any of these in the dataset finder brings you back here.
Study design
6 conditions, mostly in triplicate
Panc-Smad4OFF_m ×3
Panc-Smad4ON_m ×3
Lung-Smad4OFF_m ×3
Lung-Smad4ON_m ×3
Liv-Smad4OFF_m ×2
Liv-Smad4ON_m ×2
Supports a between-group comparison across 16 samples.
6 replicated groups read from 16 sample titles; they account for 16 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM7849476 Panc-Smad4OFF_m1
- GSM7849477 Panc-Smad4OFF_m2
- GSM7849478 Panc-Smad4OFF_m3
- GSM7849479 Panc-Smad4ON_m1
- GSM7849480 Panc-Smad4ON_m2
- GSM7849481 Panc-Smad4ON_m3
- GSM7849482 Liv-Smad4OFF_m1
- GSM7849483 Liv-Smad4OFF_m2
- GSM7849484 Liv-Smad4ON_m1
- GSM7849485 Liv-Smad4ON_m2
- GSM7849486 Lung-Smad4OFF_m1
- GSM7849487 Lung-Smad4OFF_m2
- GSM7849488 Lung-Smad4OFF_m3
- GSM7849489 Lung-Smad4ON_m1
- GSM7849490 Lung-Smad4ON_m2
- GSM7849491 Lung-Smad4ON_m3
Similar datasets
- GSE254919 Extracellular vesicles from obese visceral adipose promote pancreatic cancer development and resistance to immune checkpoint blockade therapy [ATAC-seq] 12 samples
- GSE279088 Molecular dynamics driving phenotypic divergence among KRAS mutants in pancreatic tumorigenesis [ATAC-Seq] 74 samples
- GSE264614 Emerging cooperativity between Oct4 and Sox2 governs the pluripotency network in mouse early embryos [ATAC-seq] 44 samples
- GSE302858 Multi-tier signaling and epigenomic reprogramming drive microglial inflammatory states and functions associated with demyelination [ATAC-seq] 42 samples
- GSE304037 Decoupling oxidative resilience from reprogramming to rejuvenate the RPE and restore vision [GSTA4_ATAC-seq_1] 42 samples
- GSE298001 Stage-specific Epigenetic Priming Amplifies Gene Activation During Lineage Commitment [ATAC-Seq] 36 samples
- GSE318435 ATAC-seq of the granulopoiesis lineage from different organs 34 samples
- GSE294103 SIRT6 Overexpression Counteracts Chromatin Aging [ATAC-Seq_tg] 28 samples
Share this dataset
Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.