ArticleFrontiers in oncology2026
VANGL1 links angiogenesis-stemness programs and tumor microenvironment remodeling: a pan-cancer, multi-omics study with translational validation.
Article in Frontiers in oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: The tumor microenvironment (TME) critically determines cancer progression, yet master regulators orchestrating microenvironmental remodeling across malignancies remain elusive. VANGL1, a core planar cell polarity component, has been implicated in tissue morphogenesis, but its pan-cancer landscape and TME regulatory mechanisms are unexplored. Methods: We conducted comprehensive pan-cancer analysis of VANGL1 across 33 tumor types using bulk transcriptomic, single-cell RNA sequencing, and spatial transcriptomic datasets. Intercellular communication was dissected using CellChat. Functional mechanisms were investigated through PPI networks, CancerSEA, and GSEA. Experimental validation employed loss-of-function studies in PC9, HCT116, and Bel7402 cells, patient-derived tumor organoids, and hepatocellular carcinoma stem cell-derived xenografts. Results: VANGL1 was significantly upregulated across solid tumors and as-sociated with poor prognosis. Single-cell analysis revealed VANGL1 Conclusions: Our study identifies VANGL1 as a pan-cancer master regulator integrating cancer stemness, angio-genesis, and microenvironmental remodeling, establishing therapeutic rationale for targeting the VANGL1-driven TME niche.
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