Excel · study · 2026
IGFBP5 Derived From Endothelial Cells Drive Vascular Invasion and Liver Metastasis of Colorectal Cancer by Activating the ITGB3/PI3K/AKT Axis
Listed in NCBI GEO
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).
Description
Here, we found that vascular invasion (VascI) is strongly associated with distant metastasis and poor prognosis in CRC patients. 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).
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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.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE333nnn/GSE333995 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE333995 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1473360 ncbi.nlm.nih.gov/bioproject/PRJNA1473360 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75% · RNA sequencing 75% · Sequencing 75% · Single-cell RNA sequencing 75%
Provenance · 1 source records, 11 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE333995 | 15 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:single-cell-rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |