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Co-targeting EZH2 and TEAD elicits apoptosis through tumor-intrinsic innate immune signaling in Hippo pathway-mutated cancers - RNA-seq data from genetic disruption of EZH2

GSE301957 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2025/11/25 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 12 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)
Samples
12 samples: 5 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.
Summary (written by the submitters)
TEA/TEF-domain [TEAD] inhibitors are being evaluated in clinical trials for cancers with alterations in the Hippo pathway including mesothelioma. We recently developed and showcased the potency of TEAD palmitoylation inhibitors MYF-03-69 and MYF-03-176 in mesothelioma cell lines. However, TEAD inhibition results in cell cycle arrest in cell line models with Hippo pathway alterations without inducing cell death, potentially limiting their long-term clinical efficacy.
Read the full summary ↓
Using a genome-wide CRISPR/Cas9 screen, we identified EZH2 as a critical modulator of the cellular response to TEAD inhibition. Compared to single agent treatments, EZH2i/TEADi robustly triggered apoptosis and suppressed the growth of Hippo-mutated cells in vitro and in vivo. Mechanistically, EZH2i/TEADi-treated cells exhibited heightened activation of tumor-intrinsic innate immune signaling which resulted in DNA damage and subsequent apoptosis. Taken together, we propose this novel combinatorial strategy as a potential approach to enhancing the anti-tumor efficacy of single agent TEAD targeting therapies in Hippo pathway altered tumors. This GEO accession includes the data series associated with RNA-seq derived from pharmacologic disruption of EZH2.
This dataset
Open GSE301957 in finder → Find more human 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 GSE301957_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 PRJNA1287781 and SRA study SRP598923. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
5 conditions, mostly in duplicate
20MSTO-sgCTRL-DMSO ×2 20MSTO-EZH2-KO-DMSO ×2 20MSTO-DMSO ×2 20MSTO-TAZ ×2 20MSTO-TAZposTEAD ×2 20MSTO-sgCTRL-TEAD ×1 20MSTO-EZH2-KO-TEAD ×1

Supports a between-group comparison across 10 samples.

How we read this: 5 replicated groups read from 12 sample titles; they account for 10 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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