GEO series

CDX2 downregulation regulates intrinsic WNT pathway activation, dictating metastasis in APC and CTNNB1 wildtype colorectal cancer

GSE277663 Mus musculus (mouse) RNA-seq (gene expression) 14 samples Submitted 2025/02/03 Platform GPL21103

At a glance

RNA-seq (gene expression) · mouse · 14 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Mus musculus (mouse)
Samples: 14 samples
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: CDX2 downregulation regulates intrinsic WNT pathway activation, dictating metastasis in APC and CTNNB1 wildtype colorectal cancerOncogene · 2025

Summary (written by the submitters)

Colorectal cancer (CRC) can be divided into 4 subtypes of which consensus molecular subtype 4 (CMS4) is associated with metastasis and poor survival. Previously, we reported that the KPN mouse model resembles human CMS4. Strikingly, although tumor formation in this model is slow and limited, effective metastasis is observed. To understand this aggressive behavior, we compared two distinct in vitro KPN models, organoids and tumoroids.

Read the full summary ↓

The organoid model only carries the original mutations, while the tumoroids are derived from in vivo grown tumors that underwent selection during development. Here, we reveal that tumoroids harbor endogenous WNT pathway activity, which can be driven by tankyrase activity and Cdx2 downregulation. Importantly, WNT pathway activation was heterogeneous in nature, subject to regulation and allowed for a mixture of WNT-driven and YAP-driven cells within tumoroids. This unique type of WNT pathway activation is not crucial for colonic tumor growth, but results in metastatic spreading. Intriguingly, these findings reflect a specific subset of aggressive human CMS4 cancers that display low CDX2 expression and lack of classical WNT pathway mutations, while having a higher tendency to metastasize. Together, these data propose a novel mechanism for WNT pathway activation that drives metastasis formation in aggressive CRC.

Published in

CDX2 downregulation regulates intrinsic WNT pathway activation, dictating metastasis in APC and CTNNB1 wildtype colorectal cancer

Wouters VM, Helderman RFCPA, Cameron K et al. · Oncogene 2025 · PMID 40189705 · doi:10.1038/s41388-025-03365-5

This dataset

Open GSE277663 in finder → Find more mouse RNA-seq 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 GSE277663_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: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1163318 and SRA study SRP533844. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40189705) ↗

Samples in this study

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+ 14 more — browse all 14 samples with per-sample file links →

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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.