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A plastic EMP1⁺ to LGR5⁺ cell state conversion as a therapeutic bypass to KRAS-G12D inhibition in metastatic colorectal cancer

GSE304518 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 12 samples Submitted 2025/09/29 Platform GPL19057
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 12 samples

What it is
ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism
Mus musculus (mouse)
Samples
12 samples: 6 conditions, mostly in duplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
A Plastic EMP1+ to LGR5+ Cell State Conversion as a Bypass to KRASG12D Pharmacologic Inhibition in Metastatic Colorectal CancerCancer discovery · 2026
Summary (written by the submitters)
Most patients with metastatic colorectal cancer (mCRC) ultimately succumb to the disease due to a lack of effective therapeutic options. A new generation of inhibitors targeting the oncogene KRAS holds promise for treating mCRC and are currently under clinical investigation. In this study, we explore the activity of a small molecule KRAS inhibitor, RM-044, which covalently binds to the G12D mutation in the active (ON) conformation of KRAS.
Read the full summary ↓
We found that despite robust inhibition of the KRAS signaling pathway, RM-044 exhibited limited therapeutic efficacy in patient-derived models of mCRC. Instead, liver metastases treated with RM-044 transitioned from a transcriptionally poor-prognosis-associated Emp1⁺ cell state to a WNT-driven Lgr5⁺ stem cell-like state that supported tumor growth even in the absence of KRAS-G12D activity. This plastic conversion occurred within hours of treatment, involved a switch in transcription factor usage, and did not require extensive chromatin remodeling. To explore vulnerabilities of RM-044–treated metastases, we engineered mCRC models to express the diphtheria toxin receptor under control of the Lgr5 locus. Enforced conversion of CRC cells to the Lgr5⁺ state via KRAS-G12D inhibition, followed by targeted ablation of this population using diphtheria toxin, produced strong therapeutic effects in the liver metastatic context.
Published in
A Plastic EMP1+ to LGR5+ Cell State Conversion as a Bypass to KRASG12D Pharmacologic Inhibition in Metastatic Colorectal Cancer
Centonze A, Roura AJ, Novillo-Font M et al. · Cancer discovery 2026 · PMID 41128661 · doi:10.1158/2159-8290.CD-25-0679
This dataset
Open GSE304518 in finder → Find more mouse ChIP / ATAC / CUT&Tag datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE304518_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1301422 and SRA study SRP606440. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41128661) ↗
Study design
6 conditions, mostly in duplicate
AKTP MTO93 mouse tumor organoids, vehicle con… ×2 AKTP MTO93 mouse tumor organoids, vehicle con… ×2 AKTP MTO93 mouse tumor organoids, vehicle con… ×2 AKTP MTO93 mouse tumor organoids, RM-044, H3K… ×2 AKTP MTO93 mouse tumor organoids, RM-044, IgG, ×2 AKTP MTO93 mouse tumor organoids, RM-044, Jun… ×2

Supports a between-group comparison across 12 samples.

How we read this: 6 replicated groups read from 12 sample titles; they account for 12 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
Datasets on a similar topic

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