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Chemotherapy-driven de novo Wnt pathway activation dictates a dynamic shift to a drug-tolerant state in breast cancer cells

GSE254558 Homo sapiens (human) RNA-seq (gene expression) 46 samples Submitted 2025/09/25 Platform GPL20301
At a glance

RNA-seq (gene expression) · human · 46 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
Homo sapiens (human)
Topic
Breast cancerThis series is part of our curated briefing on it.
Samples
46 samples: 9 conditions, mostly with about 6 replicates eachGroups 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
Chemotherapy-Treated Breast Cancer Cells Activate the WNT Signaling Pathway to Enter a Diapause-Like Early Persister StateCancer research · 2026
Summary (written by the submitters)
Triple-negative breast cancer (TNBC) initially exhibits a robust response to chemotherapy; however paradoxically, the treatment enriches a population of drug-tolerant persister (DTP) cells, which are known to drive therapy resistance. Therefore, it is crucial to, foremost, identify and subsequently target the signaling pathways implicated in therapy-induced drug resistance and the emergence of DTP cells.
Read the full summary ↓
In this study, by combining the use of human TNBC cell lines, 3D patient-derived organoid models, and in vivo xenograft models, we identified activation of the Wnt/β-catenin signaling pathway as a common mechanism underlying early DTP cell(s) enrichment in response to different chemotherapeutic agents. Live-cell imaging using Wnt-reporter TNBC cell lines validated diverse patterns of Wnt-transcriptional enrichment, encompassing both intrinsic selection and acquired de novo activation in response to chemotherapy treatment. Purification of differential Wnt-transcriptional populations revealed that post-treatment WntLow cells succumb to apoptosis, while, in contrast, chemotherapy-treated Wnt-active (WntHigh) cells adopt stem cell-like traits, exhibit reduced proliferation, and are, in turn, refractory to treatment. The transition to a post-treatment WntHigh state is orchestrated by increased expression of Wnt ligands, R-spondins, and factors facilitating Wnt ligand secretion, such as PORCN. Consequently, genetic or concomitant - but not sequential - pharmacological inhibition of Wnt ligand secretion alongside chemotherapy prevents treatment-induced WntHigh enrichment and sensitizes TNBC tumors to chemotherapy. Taken together, these observations provide a strong rationale for testing dual treatment comprising chemotherapy and Wnt ligand secretion inhibitors in clinical trials, extending to all TNBC patients.
Published in
Chemotherapy-Treated Breast Cancer Cells Activate the WNT Signaling Pathway to Enter a Diapause-Like Early Persister State
El Laithy Y, Abreu De Oliveira WA, Pabba A et al. · Cancer research 2026 · PMID 41117706 · doi:10.1158/0008-5472.CAN-24-4165
This dataset
Open GSE254558 in finder → Find more human RNA-seq datasets → Breast cancer landscape →
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 GSE254558_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 PRJNA1071047 and SRA study SRP486790. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41117706) ↗
Study design
9 conditions, mostly with about 6 replicates each
MDA-MB-231dTOP CAR NEG ×8 MDA-MB-231dTOP CAR POS ×8 MDA-MB-231dTOP UNT NEG ×6 MDA-MB-231dTOP DOC NEG ×6 MDA-MB-231dTOP DOC POS ×6 MDA-MB-231dTOP UNT POS ×4 MDA-MB-231 DOC D3 ×3 MDA-MB-231 CAR D3 ×3 +1 more

Supports a between-group comparison across 46 samples.

How we read this: 9 replicated groups read from 46 sample titles; they account for 46 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

+ 6 more — browse all 46 samples with per-sample file links →

More Breast cancer datasets

Search all human RNA-seq datasets in GEO →

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.