GEO series

Targeting Fatty Acid Oxidation Enhances Response to HER2-targeted Therapy

GSE254622 Mus musculus (mouse) RNA-seq (gene expression) 11 samples Submitted 2024/07/08 Platform GPL17021

At a glance

RNA-seq (gene expression) · mouse · 11 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: 11 samples: 11 samples, each with a distinct title — no replicated groupsGroups 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 fatty acid oxidation enhances response to HER2-targeted therapyNature communications · 2024

Summary (written by the submitters)

Metabolic reprogramming is a hallmark of tumorigenesis and includes alterations in glucose and fatty acid metabolism. In this study, we investigated the role of Carnitine palmitoyl transferase 1A (CPT1A), a key enzyme in fatty acid oxidation (FAO), in the induction of HER2+ (Human Epidermal growth factor 2, ErbB2) breast cancer. Using an ErbB2+ genetically engineered mouse models, we found that ablation of CPT1A delayed tumor onset and reduced tumor growth, angiogenesis, and metastatic capacity.

Read the full summary ↓

CPT1A-deficient ErbB2+ cells exhibited impaired mitochondrial function, leading to a reliance on the tricarboxylic acid cycle to reduce NAD+/FAD for energy production. Consequently, loss of CPT1A resulted in glucose dependency and an inability to metabolize fats. CPT1A-deficient ErbB2+ tumor cells exhibited increased oxidative stress and upregulated nuclear factor erythroid 2-related factor 2 (NRF2) activity. Inhibiting NRF2 or silencing its expression reduced proliferation and glucose consumption in CPT1A-deficient cells. In pre-clinical models of ErbB2+ breast cancer, combining a ketogenic diet with an anti-ErbB2 monoclonal antibody in the context of CPT1A deficiency significantly reduced tumor growth and increased survival. Furthermore, combining the ketogenic diet with CPT1A ablation suppressed tumor growth, enhanced apoptosis, and reduced lung metastasis. Additionally, using an immunocompetent model, we provide evidence that CPT1A inhibition attenuated tumor growth and proliferation by promoting an antitumor immune microenvironment that enhanced the efficacy of ErbB2 targeted therapy. These findings provide insight into the metabolic rewiring in HER2+ breast cancer and highlight the potential of targeting fatty acid oxidation and employing metabolic interventions as a combination therapy strategy for HER2+ breast cancer patients, including those resistant to standard treatment regimes.

Published in

Targeting fatty acid oxidation enhances response to HER2-targeted therapy

Nandi I, Ji L, Smith HW et al. · Nature communications 2024 · PMID 39097623 · doi:10.1038/s41467-024-50998-3

This dataset

Open GSE254622 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 GSE254622_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 PRJNA1071151 and SRA study SRP486919. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39097623) ↗

Study design

11 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 11 sample titles: 11 distinct titles with little repetition. 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

GSM8047339 Mammary epithelial tumor-derived cells from NIC mice without conditional Cpt1a alleles_1A [KO_1922A_biol rep 1]
GSM8047340 Mammary epithelial tumor-derived cells from NIC mice without conditional Cpt1a alleles_1B [KO_1922B_biol rep 2]
GSM8047341 Mammary epithelial tumor-derived cells from NIC mice without conditional Cpt1a alleles_2A [KO_1925A_biol rep 1]
GSM8047342 Mammary epithelial tumor-derived cells from NIC mice without conditional Cpt1a alleles_2B [KO_1925B_biol rep 2]
GSM8047343 Mammary epithelial tumor-derived cells from NIC mice without conditional Cpt1a alleles_3B [KO_2768B_biol rep 2]
GSM8047344 Mammary epithelial tumor-derived cells from NIC mice without conditional Cpt1a alleles_4A [KO_4258A_biol rep 1]
GSM8047345 Mammary epithelial tumor-derived cells from NIC mice without conditional Cpt1a alleles_4B [KO_4258B_biol rep 2]
GSM8047346 Mammary epithelial tumor-derived cells from wild-type NIC mice with conditional Cpt1a alleles_1A [WT_5257A_biol rep 1]
GSM8047347 Mammary epithelial tumor-derived cells from wild-type NIC mice with conditional Cpt1a alleles_1B [WT_5257B_biol rep 2]
GSM8047348 Mammary epithelial tumor-derived cells from wild-type NIC mice with conditional Cpt1a alleles_2A [WT_8905A_biol rep 1]
GSM8047349 Mammary epithelial tumor-derived cells from wild-type NIC mice with conditional Cpt1a alleles_2B [WT_8905B_biol rep 2]

Datasets on a similar topic

GSE186648 Skeletal muscle mRNA expression in 25 mice with or without genetic defects of mitochondrial fatty acid oxidation (Acadl and Acadvl knockout) using RNA sequencing. 25 samples shares oxidation, fatty, acid
GSE264369 Fatty acid oxidation downregulation in alveolar epithelial 2 cells promotes acute lung injury in obesity 18 samples shares oxidation, fatty, acid
GSE315303 Pygo2 Loss Induces Tertiary Lymphoid Structure Formation and Enhances Immunotherapy and Castration Responses in Prostate Cancer 22 samples shares enhances, therapy
GSE263625 Microglial reprogramming enhances antitumor immunity and immunotherapy response in melanoma brain metastases 19 samples shares enhances, therapy
GSE271367 Enhancing tumor response to adoptive T cell therapy by targeting PHD2/3 in CD8 T cells 18 samples shares targeting, therapy
GSE295426 Targeting branched-chain amino acids alleviates pulmonary fibrosis [RNA-seq] 54 samples shares targeting, acid
GSE281467 Coactivation of innate immune suppressive cells induces acquired resistance against cancer immunotherapy targeting the innate immune system [TIICs RNA-seq] 30 samples shares targeting, therapy
GSE274960 Targeting NTRK1 Enhances Immune Checkpoint Inhibitor Efficacy in NTRK1 Wild-type Non-Small Cell Lung Cancer 19 samples shares targeting, enhances

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.