GEO series

A targetable PREX2/RAC1/PI3Kb signalling axis confers resistance to clinically relevant therapeutic approaches in melanoma

GSE281123 Mus musculus (mouse) RNA-seq (gene expression) 18 samples Submitted 2024/11/22 Platform GPL19057

At a glance

RNA-seq (gene expression) · mouse · 18 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: 18 samples: 6 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: Targeting the PREX2/RAC1/PI3Kβ Signaling Axis Confers Sensitivity to Clinically Relevant Therapeutic Approaches in MelanomaCancer research · 2025

Summary (written by the submitters)

Metastatic melanoma remains a major clinical challenge. Large-scale genomic sequencing of melanoma has identified bona fide activating mutations in RAC1, with mutations of its upstream regulator, the RAC-GEF PREX2, also commonly detected. Crucially, RAC1 mutations are associated with resistance to BRAF-targeting therapies. Despite the role of its homologue PREX1 in melanomagenesis, and evidence that some truncating PREX2 mutations drive increased RAC1 activity, no hotspot mutations have been identified, and the impact of PREX2 mutation remains contentious.

Read the full summary ↓

Here, we use genetically engineered mouse models and patient-derived BRAFV600E-driven melanoma cell lines to dissect the role of PREX2 in melanomagenesis and response to therapy. We show that while PREX2 is dispensable for the initiation and progression of melanoma, its loss confers sensitivity to clinically relevant therapeutics. Importantly, genetic and pharmacological targeting of the RAC1 effector kinase PI3Kβ phenocopies PREX2 loss, sensitizing our model systems to therapy. Our data reveal a druggable PREX2/RAC1/PI3Kβ signalling axis in BRAF-mutant melanoma that could be exploited clinically.

Published in

Targeting the PREX2/RAC1/PI3Kβ Signaling Axis Confers Sensitivity to Clinically Relevant Therapeutic Approaches in Melanoma

Ford CA, Koludrovic D, Centeno PP et al. · Cancer research 2025 · PMID 39636745 · doi:10.1158/0008-5472.CAN-23-2814

This dataset

Open GSE281123 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 GSE281123_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 PRJNA1182338 and SRA study SRP543307. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39636745) ↗

Study design

6 conditions, mostly in triplicate

BPten Melanoma 6244/8835 ×3 BPten Melanoma Vehicle ×3 BPten Melanoma 6244/8186 ×3 BPten Melanoma 8186 ×3 BPten Melanoma 6244 ×3 BPten Melanoma 8835 ×3

Supports a between-group comparison across 18 samples.

How we read this: 6 replicated groups read from 18 sample titles; they account for 18 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

GSM8611281 BPten Melanoma 6244/8835 rep1 BPten Melanoma 6244/8835
GSM8611282 BPten Melanoma Vehicle rep1 BPten Melanoma Vehicle
GSM8611283 BPten Melanoma 6244/8186 rep1 BPten Melanoma 6244/8186
GSM8611284 BPten Melanoma 6244/8835 rep2 BPten Melanoma 6244/8835
GSM8611285 BPten Melanoma 6244/8835 rep3 BPten Melanoma 6244/8835
GSM8611286 BPten Melanoma Vehicle rep2 BPten Melanoma Vehicle
GSM8611287 BPten Melanoma 8186 rep1 BPten Melanoma 8186
GSM8611288 BPten Melanoma 6244 rep1 BPten Melanoma 6244
GSM8611289 BPten Melanoma 8835 rep1 BPten Melanoma 8835
GSM8611290 BPten Melanoma 8835 rep2 BPten Melanoma 8835
GSM8611291 BPten Melanoma 8186 rep2 BPten Melanoma 8186
GSM8611292 BPten Melanoma 6244 rep2 BPten Melanoma 6244
GSM8611293 BPten Melanoma Vehicle rep3 BPten Melanoma Vehicle
GSM8611294 BPten Melanoma 6244/8186 rep2 BPten Melanoma 6244/8186
GSM8611295 BPten Melanoma 6244/8186 rep3 BPten Melanoma 6244/8186
GSM8611296 BPten Melanoma 6244 rep3 BPten Melanoma 6244
GSM8611297 BPten Melanoma 8835 rep3 BPten Melanoma 8835
GSM8611298 BPten Melanoma 8186 rep3 BPten Melanoma 8186

Datasets on a similar topic

GSE307773 Oncogenic MAPK signalling induces epithelial cell state change and therapeutic resistance in vivo [RNA-Seq] 175 samples shares therapeutic, resistance
GSE293450 Hypoxia shapes both therapeutic response and resistance in metastatic clear cell renal cell carcinoma 38 samples shares therapeutic, resistance
GSE307774 Oncogenic MAPK signalling induces epithelial cell state change and therapeutic resistance in vivo [scRNA-Seq] 29 samples shares therapeutic, resistance
GSE279935 Gli2 Facilitates Tumor Immune Evasion and Immunotherapeutic Resistance by Coordinating Wnt Ligand and Prostaglandin Signaling [Cell_Line_RNAseq] 12 samples shares therapeutic, resistance
GSE305462 Rac1 palmitoylation is required for cardiac stress adaptation and regulation of Protein Kinase A signaling 18 samples shares rac1
GSE298273 Tumor-derived RAC1A159V mutation promotes an immunosuppressive tumor microenvironment that represses response to immune checkpoint inhibitor [RNA-Seq] 12 samples shares rac1
GSE319694 Myeloid Piezo1 Drives Cardiac Repair Through Orai1–Rac1-Dependent Efferocytosis 10 samples shares rac1
GSE223323 Enterocyte like differentiation defines metabolic gene signatures of CMS3 colorectal cancers and provides therapeutic vulnerability 148 samples shares therapeutic

Search all mouse 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.