GEO series

IGFBP5 Derived From Endothelial Cells Drive Vascular Invasion and Liver Metastasis of Colorectal Cancer by Activating the ITGB3/PI3K/AKT Axis

GSE333995 Homo sapiens (human) Single-cell RNA-seq 9 samples Submitted 2026/07/15 Platform GPL34281

At a glance

Single-cell RNA-seq · human · 9 samples

What it is: Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism: Homo sapiens (human)
Topic: Colorectal cancerThis series is part of our curated briefing on it.
Samples: 9 samples
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)

Vascular invasion is a critical step in colorectal cancer (CRC) metastasis, but how specific cells in the tumor microenvironment (TME) regulate this process remains unclear, particularly the role of endothelial cells (ECs). Here, we found that vascular invasion (VascI) is strongly associated with distant metastasis and poor prognosis in CRC patients.

Read the full summary ↓

Analysis of single-cell RNA sequencing (scRNA- seq) data from 8 colorectal cancer liver metastases (CRLMs), included 4 VascI+ CRLMs and 4 VascI- CRLMs, and identified 10 distinct EC subpopulations. Notably, an IGFBP5+ tipECs significantly enriched in VascI+ CRLMs. High IGFBP5 expression correlated with VascI+ status and poor patient prognosis. Functionally, IGFBP5 overexpression (OE) in human umbilical vein endothelial cells (HUVECs) enhanced EC migration, tube formation, barrier disruption, and endothelial-to-mesenchymal transition (EndMT). In co-culture system, IGFBP5-OE ECs promoted malignant epithelial cells (MCs) proliferation, migration, and adhesion, and accelerated the growth of patient-derived CRC organoids. Mechanistically, RNA sequencing nominated ITGB3 as a key downstream effector, with activation of the PI3K/AKT signaling pathway. We confirmed a direct ligand-receptor interaction between EC-derived IGFBP5 and ITGB3 on MCs using multiplex immunofluorescence (mIF), co-immunoprecipitation (CO-IP), and proximity ligation assays (PLA). This interaction activated PI3K/AKT signaling in MCs, driving aggressive behavior both in vitro and in vivo, an effect abolished by ITGB3 silencing in MCs. Our findings identify IGFBP5-OE ECs as a key driver of VascI and liver metastasis in CRC via the ITGB3/PI3K/Akt axis, highlighting a potential therapeutic target to suppress metastatic progression.

This dataset

Open GSE333995 in finder → Find more human RNA-seq datasets → Colorectal 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 GSE333995_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1473360 and SRA study SRP705889. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Samples in this study

The sample list for this study is not cached yet. Press Load samples and it will be fetched from NCBI.

+ 9 more — browse all 9 samples with per-sample file links →

More Colorectal cancer datasets

GSE250000 Bulk RNA-sequencing of transduced colorectal cancer cell line HCT-116 and breast cancer cell line MCF-7 overexpressing full-lenght p53β or p53β-stop-lost. 4 samples same disease briefing · shares colorectal
GSE12032 Inherent gene signature of stage II and III colorectal cancer leads in individual recurrence 198 samples same disease briefing · shares colorectal
GSE109308 Single-cell transcriptomic survey of adenomatous polyposis patients with germline APC mutations 97 samples same disease briefing
GSE110009 Single cell transcriptome landscape of primary and metastatic tumor in colon cancer 76 samples same disease briefing
GSE269369 LIN28B-mediated activation of the PI3K/AKT pathway promotes metastasis and unravels a new therapeutic vulnerability in colorectal cancer 18 samples shares pi3k, akt, metastasis, colorectal
GSE316535 POFUT1 Serves as an Independent Prognostic Factor and Therapeutic Target by Activating the PI3K/AKT Pathway in Glioma 14 samples shares pi3k, akt, activating
GSE310085 Sulforaphane Inhibits Colorectal Cancer Progression via PI3K/AKT/mTOR and HIF-1α Suppression with Enhanced Efficacy under Hypoxia 9 samples shares pi3k, akt, colorectal
GSE290045 Colorectal cancer-derived osteopontin rewires macrophages into a pro-metastatic M2 state via the PI3K/AKT/CSF1-CSF1R axis 6 samples shares pi3k, akt, colorectal

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.