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Loss of WWOX Drives Cutaneous Squamous Cell Carcinoma (cSCC) through Regulating EMT [RNA-Seq]

GSE300269 Mus musculus (mouse) RNA-seq (gene expression) 20 samples Submitted 2026/04/13 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 20 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
20 samples: 7 conditions, mostly in triplicateGroups 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
WWOX maintains epidermal identity and suppresses EMT to prevent aggressive cutaneous squamous cell carcinomaProceedings of the National Academy of Sciences of the United States of America · 2026
Summary (written by the submitters)
Cutaneous Squamous Cell Carcinoma (cSCC) is the second most common skin cancer, with a rising incidence in recent years. Through protein-protein interactions, the WW domain-containing oxidoreductase (WWOX) has been found to be a key player in many cellular processes, including DNA repair, apoptosis, metabolism, and transcriptional regulation.
Read the full summary ↓
WWOX loss has been reported in many malignancies, including cSCC, suggesting a tumor suppressor role, but its function as a skin cancer antagonist and the underlying molecular mechanisms are not yet fully understood. To better understand WWOX's role in cSCC, we generated K14-Cre;Wwox;Trp53 conditional knock-out mice, leading to the development of cSCC. Strikingly, mice with ablated WWOX developed cSCC with increased penetrance and earlier onset. Characterization of cSCC morphology, immune markers, and transcriptional signatures revealed poorly differentiated cSCC with epithelial-to-mesenchymal transition (EMT) traits in tumors lacking WWOX compared to their controls. The hyperplastic phenotype of the epidermis in conditionally Wwox-knock-out mice was observed at an early age and impacted the surrounding microenvironment as well. Based on WWOX's known interaction with and stabilization of the transcription factor p63, we proposed that epidermal WWOX loss reduces p63 levels, destabilizing the tissue's epithelial integrity. Indeed, our findings confirmed this mechanism, demonstrating that diminished p63 impairs the epidermal protective barrier and accelerates the progression of aggressive cSCC. The WWOX-p63 correlation was also observed in human cSCC samples, inversely related to tumor stage. These findings were further supported in keratinocytes and cSCC human cell line models, where WWOX deficiency led to reduced p63 expression, concomitant with enhanced tumorigenic potential and migratory capacity.
Published in
WWOX maintains epidermal identity and suppresses EMT to prevent aggressive cutaneous squamous cell carcinoma
Bidany-Mizrahi T, Maroun K, Mancini M et al. · Proceedings of the National Academy of Sciences of the United States of America 2026 · PMID 41984841 · doi:10.1073/pnas.2534844123
This dataset
Open GSE300269 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 GSE300269_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 PRJNA1280001 and SRA study SRP593331. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41984841) ↗
Study design
7 conditions, mostly in triplicate
tdTom+ cells of cSCC from K14cre;p53fl/fl mic… ×3 tdTom+ cells of cSCC from K14cre;Wwoxfl/fl;p5… ×3 tdTom+ cells of young Wild-type epidrmis, ×3 tdTom+ cells of young K14cre;Wwoxfl/fl epidrm… ×3 tdTom+ cells of young K14cre;p53fl/fl epidrmi… ×3 tdTom+ cells of young K14cre;Wwoxfl/fl;p53fl/… ×3 tdTom+ cells of old Wild-type epidrmis, ×2

Supports a between-group comparison across 20 samples.

How we read this: 7 replicated groups read from 20 sample titles; they account for 20 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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