GEO series

Lysyl oxidase inhibition disrupts mitochondrial homeostasis to create vulnerability to ferroptosis in TNBC

GSE312563 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2026/07/06 Platform GPL11154

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)
Topic: Breast cancerThis series is part of our curated briefing on it.
Samples: 12 samples: 6 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)

High metabolic heterogeneity and plasticity of triple-negative breast cancer (TNBC) contribute to therapy resistance, necessitating identification of novel therapeutic vulnerabilities. Here, we identify non-canonical functions of the ECM remodeler, lysyl oxidase (LOX), in regulating glucose metabolism and mitochondrial homeostasis and show that inhibiting LOX generates targetable vulnerability to ferroptosis.

Read the full summary ↓

Mechanistically, LOX interacts with PARKIN and its upstream kinase PINK1, which we identified as a substrate of LOX. LOX-mediated PINK1 oxidation suppresses PARKIN phosphorylation, stabilizing HIF-1α and increasing glycolysis. Concomitantly, LOX inhibits PARKIN-mediated mitophagy and maintains mitochondria-ER contacts through VDAC1 stabilization while the LOX-HSP90 complex promotes mitochondrial Ca2+ transport and ATP production. Inhibiting LOX suppresses glycolysis, disrupts mitochondrial dynamics, reduces OXPHOS and GPX4/FSP1, and induces compensatory DHODH activity. Our ‘one-two punch’ approach combining LOX inhibition with clinical DHODH inhibitor suppresses tumor growth in vivo in chemo-free setting. Notably, LOX protein correlates with HIF-1α/GLUT1/GPX4 in TNBC patient tumors, supporting its clinical relevance.

This dataset

Open GSE312563 in finder → Find more human RNA-seq datasets → Breast cancer landscape →

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 GSE312563_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 PRJNA1374186 and SRA study SRP651455. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

6 conditions, mostly in duplicate

MDA_231_24h ×2 MDA_231_V ×2 MDA_436_24h ×2 MDA_436_V ×2 HS_24h ×2 HS_V ×2

Supports a between-group comparison across 12 samples.

How we read this: 6 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

GSM9348621 MDA_231_24h_rep1 MDA_231_24h
GSM9348622 MDA_231_24h_rep2 MDA_231_24h
GSM9348623 MDA_231_V_rep1 MDA_231_V
GSM9348624 MDA_231_V_rep2 MDA_231_V
GSM9348625 MDA_436_24h_rep1 MDA_436_24h
GSM9348626 MDA_436_24h_rep2 MDA_436_24h
GSM9348627 MDA_436_V_rep1 MDA_436_V
GSM9348628 MDA_436_V_rep2 MDA_436_V
GSM9348629 HS_24h_rep1 HS_24h
GSM9348630 HS_24h_rep2 HS_24h
GSM9348631 HS_V_rep1 HS_V
GSM9348632 HS_V_rep2 HS_V

More Breast cancer datasets

GSE104193 Hypoxia-mediated translational activation of ITGB3 in breast cancer cells enhances TGF-β signalling and malignant features in vitro and in vivo 32 samples same disease briefing
GSE104675 Role for the Transcriptional Activator ZRF1 in Breast Cancer Progression and Endocrine Resistance 6 samples same disease briefing
GSE10885 An integromic analysis reveals that metaplastic carcinomas are distinct from basal-like tumors. 244 samples same disease briefing
GSE10886 A Supervised Risk Predictor of Breast Cancer Based on Biological Subtypes 226 samples same disease briefing
GSE11121 The humoral immune system has a key prognostic impact in node-negative breast cancer 200 samples same disease briefing
GSE307575 A covalent fragment screen identifies ferroptosis induced by GPX4 inhibition as a vulnerability of senescent cells 11 samples shares vulnerability, ferroptosis, inhibition
GSE286057 Ovarian cancer metastasis to the human omentum disrupts organ homeostasis and induces fundamental tissue reprogramming 36 samples shares homeostasis, disrupts
GSE273492 Selective NSD2 Inhibition Reveals an Epigenetic Vulnerability of KRAS-Driven Cancers [RNA-Seq] 36 samples shares vulnerability, inhibition

Search all human 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.