VANGL1 links angiogenesis–stemness programs and tumor microenvironment remodeling: a pan-cancer, multi-omics study with translational validation

To investigate the expression landscape, clinical relevance, and mechanistic role of VANGL1 in tumor progression across various cancer types.

VANGL1 was significantly upregulated in solid tumors and associated with poor prognosis.
Single-cell analysis indicated enhanced communication between VANGL1+ malignant cells and stromal components.
VANGL1 integrated Wnt/Notch/mTOR signaling with cancer stemness and angiogenesis.
Knock-down of VANGL1 suppressed tumor cell proliferation, migration, and invasion in vitro, and reduced tumor growth and angiogenesis in vivo.

VANGL1 serves as a master regulator linking cancer stemness, angiogenesis, and tumor microenvironment remodeling across multiple cancer types.

The study's exploratory nature limits the generalizability of findings without cross-cancer false discovery rate correction.
Potential biases in data acquisition and analysis methods may affect results.

VANGL1 is identified as a pan-cancer therapeutic target, highlighting its role in the tumor microenvironment.