GEO series

Loss of the Aryl Hydrocarbon Receptor (AhR) Promotes Cancer Cells Resistance to BRAFV600E Targeted Therapies. [RNA-Seq]

GSE286108 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2025/01/12 Platform GPL30173

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: 3 × C_NTC vs 3 × DT_NTC vs 3 × C_AH vs 3 × DT_AHGroups 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: Loss of the aryl hydrocarbon receptor promotes cancer cell resistance to BRAFV600E targeted therapiesSignal transduction and targeted therapy · 2025

Summary (written by the submitters)

Predicting a patient’s response to chemotherapies and identifying additional molecular targets to improve treatment efficacy are major objectives in cancer research. BRAFV600E inhibitors targeting the MAP kinase pathway showed promising initial clinical results in thyroid cancers (TCs) for metastatic or recurrent tumors refractory to radioiodine treatments.

Read the full summary ↓

BRAFV600E-targeted therapies have also been approved by the FDA for the treatment of some unresectable or metastatic BRAFV600E+ solid tumors. Still, for most patients, the response to BRAFV600E blocking therapy is transient due to cell proliferation reactivation through escape pathways. We performed a genome-wide CRISPR screen to reveal targets in TCs that facilitate resistance or sensitize thyroid cancer cells to inhibitors of the MAP kinase pathway. Among the genes that consistently altered MAPK inhibitor treatment response, we identified the Aryl hydrocarbon Receptor (AhR) and its molecular partner, the AhR nuclear translocator (ARNT). The AHR-ARNT heteroduplex is an environmental sensor that integrates extracellular, endogenous, and metabolic signals to equilibrate cell activity. Inactivation of AhR or ARNT increased TC cells' resistance to targeted therapies. Our study revealed that AhR-deficient cancer cells expressed elevated activity in genes linked to the TGFβ-mediated SMAD2/3 pathway after drug treatment. Our results suggest that SMAD2/3 competes to bind ARNT and that the loss of AhR gives cancer cells a potent escape pathway to targeted therapies, counteracting MAPK inhibition with SMAD activation to sustain cancer cell proliferation.

Published in

Loss of the aryl hydrocarbon receptor promotes cancer cell resistance to BRAFV600E targeted therapies

Zerfaoui M, Patel D, Zhang Y et al. · Signal transduction and targeted therapy 2025 · PMID 40360477 · doi:10.1038/s41392-025-02235-6

This dataset

Open GSE286108 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 GSE286108_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 PRJNA1207950 and SRA study SRP556018. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40360477) ↗

Study design

3 × C_NTC vs 3 × DT_NTC vs 3 × C_AH vs 3 × DT_AH

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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

GSM8717840 C_NTC_01 C_NTC
GSM8717841 C_NTC_02 C_NTC
GSM8717842 C_NTC_03 C_NTC
GSM8717843 DT_NTC_01 DT_NTC
GSM8717844 DT_NTC_02 DT_NTC
GSM8717845 DT_NTC_03 DT_NTC
GSM8717846 C_AHR_01 C_AH
GSM8717847 C_AHR_02 C_AH
GSM8717848 C_AHR_03 C_AH
GSM8717849 DT_AHR_01 DT_AH
GSM8717850 DT_AHR_02 DT_AH
GSM8717851 DT_AHR_03 DT_AH

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