GEO series

LHPP expression in triple-negative breast cancer promotes tumor growth and metastasis by modulating the tumor microenvironment

GSE281450 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2025/11/07 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)
Topic: Breast cancerThis series is part of our curated briefing on it.
Samples: 12 samples: 3 × MDA-MB-231, WT, biol vs 3 × MDA-MB-231, LHPP KO, biol vs 3 × MCF7, WT, biol vs 3 × MCF7, LHPP KO, biolGroups 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: LHPP expression in triple-negative breast cancer promotes tumor growth and metastasis by modulating the tumor microenvironmentProceedings of the National Academy of Sciences of the United States of America · 2025

Summary (written by the submitters)

Triple-negative breast cancer (TNBC) is a highly aggressive and metastatic form of breast cancer that lacks an effective targeted therapy. To identify potential therapeutic targets, we investigated the phosphohistidine phosphatase, LHPP, which has been implicated in the development of several types of cancer. However, the full significance of LHPP in cancer progression remains unclear due to our limited understanding of its molecular mechanism.

Read the full summary ↓

We found that levels of the LHPP phosphohistidine phosphatase were significantly increased in human breast cancer patients compared to normal adjacent tissues, with the highest levels in the TNBC subtype. When LHPP was knocked out in the MDA-MB-231 human TNBC cell line, cell proliferation, wound healing capacity, and invasion were significantly reduced. However, LHPP knockout in TNBC cells did not significantly affect overall phosphohistidine protein levels. Interestingly, LHPP knockout in MDA-MB-231 cells delayed tumor growth and reduced metastasis when orthotopically transplanted into mouse mammary glands. To investigate LHPP’s role in breast cancer progression, we used next-generation sequencing and proximity-labeling proteomics, and found that LHPP regulates gene expression in chemokine-mediated signaling and actin cytoskeleton organization. Depletion of LHPP reduced the presence of tumor-infiltrating macrophages in mouse xenografts. Our results support a tumor promoter role for LHPP phosphohistidine phosphatase in MDA-MB-231TNBC cells and suggest that targeting LHPP phosphatase could be a potential therapeutic strategy for TNBC.

Published in

LHPP expression in triple-negative breast cancer promotes tumor growth and metastasis by modulating the tumor microenvironment

Reina J, Vallmajo-Martin Q, Ning J et al. · Proceedings of the National Academy of Sciences of the United States of America 2025 · PMID 41343666 · doi:10.1073/pnas.2505653122

This dataset

Open GSE281450 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 GSE281450_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 PRJNA1183874 and SRA study SRP544546. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41343666) ↗

Study design

3 × MDA-MB-231, WT, biol vs 3 × MDA-MB-231, LHPP KO, biol vs 3 × MCF7, WT, biol vs 3 × MCF7, LHPP KO, biol

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

GSM8620935 MDA-MB-231, WT, biol rep 1 MDA-MB-231, WT, biol
GSM8620936 MDA-MB-231, WT, biol rep 2 MDA-MB-231, WT, biol
GSM8620937 MDA-MB-231, WT, biol rep 3 MDA-MB-231, WT, biol
GSM8620938 MDA-MB-231, LHPP KO, biol rep 1 MDA-MB-231, LHPP KO, bi…
GSM8620939 MDA-MB-231, LHPP KO, biol rep 2 MDA-MB-231, LHPP KO, bi…
GSM8620940 MDA-MB-231, LHPP KO, biol rep 3 MDA-MB-231, LHPP KO, bi…
GSM8620941 MCF7, WT, biol rep 1 MCF7, WT, biol
GSM8620942 MCF7, WT, biol rep 2 MCF7, WT, biol
GSM8620943 MCF7, WT, biol rep 3 MCF7, WT, biol
GSM8620944 MCF7, LHPP KO, biol rep 1 MCF7, LHPP KO, biol
GSM8620945 MCF7, LHPP KO, biol rep 2 MCF7, LHPP KO, biol
GSM8620946 MCF7, LHPP KO, biol rep 3 MCF7, LHPP KO, biol

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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.