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Ageing promotes metastasis via activation of the integrated stress response

GSE263688 Mus musculus (mouse) RNA-seq (gene expression) 16 samples Submitted 2026/01/23 Platform GPL19057
At a glance

RNA-seq (gene expression) · mouse · 16 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
16 samples: 4 × KPY1 vs 4 × KPY2 vs 4 × KPO1 vs 4 × KPO2Groups 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
Ageing promotes metastasis via activation of the integrated stress responseNature · 2026
Summary (written by the submitters)
Lung cancer predominantly affects older individuals, yet how physiological aging influences tumor evolution remains poorly understood. Here, we show that aging reprograms the evolutionary trajectory of KRAS-driven lung adenocarcinoma, limiting primary tumor growth while promoting metastatic dissemination through epigenetic activation of the integrated stress response (ISR).
Read the full summary ↓
The ISR effector ATF4 drives epithelial and metabolic plasticity, conferring metastatic competence. Mechanistically, aged tumor cells exhibit increased sensitivity to the PERK–eIF2α arm of the unfolded protein response, sustaining persistent ATF4 signaling. Targeting the ISR-ATF4 genetically or pharmacologically abolishes these adaptations and limits dissemination, whereas ATF4 overexpression alone is sufficient to induce metastasis. The aging–ATF4 axis imposes a dependency on glutamine metabolism, revealing a therapeutically actionable vulnerability. Clinical analyses confirm that ATF4 is enriched in aged tumors and correlates with poor survival and advanced-stage disease. Collectively, these results define epigenetic ISR–ATF4 activation as a causal driver of lineage plasticity and metastasis in aged tumors, revealing a therapeutic opportunity in older patients with lung adenocarcinoma, the most common yet understudied subset of lung cancer
Published in
Ageing promotes metastasis via activation of the integrated stress response
Patel AAH, Dzanan JJ, Ali KX et al. · Nature 2026 · PMID 41813904 · doi:10.1038/s41586-026-10216-0
This dataset
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.

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 GSE263688_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1098895 and SRA study SRP501269. Searching any of these in the dataset finder brings you back here.

Study design
4 × KPY1 vs 4 × KPY2 vs 4 × KPO1 vs 4 × KPO2

Supports a between-group comparison across 16 samples.

How we read this: 4 replicated groups read from 16 sample titles; they account for 16 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
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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.