ArticleCancer biomarkers : section A of Disease markers2024
GABPα inhibits tumor progression and angiogenesis via a novel 18-bp indel within
Article in Cancer biomarkers : section A of Disease markers, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Evaluation ofCancer management and research · 2026Article
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9 authors.
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Abstract
backgroundPathological angiogenesis is crucial for tumor progression, thus targeting neovascularization is regarded as an effective strategy for cancer therapy. Vascular endothelial growth factor (VEGF), a specific pro-vascular endothelial regulator, contributes to aberrant tumor angiogenesis.
objectiveTo identify sequence polymorphisms of VEGF gene and the effects on breast cancer.
methodsProtein-DNA binding was validated by EMSA and ChIP assay. Gene expression levels were detected by qPCR and western blot. The CCK-8, wound healing and transwell assays were used to assess proliferation, migration, and invasion. Tube formation, CAM, ELISA and IHC assays were performed to evaluate tumor angiogenesis.
resultsA novel 18-bp indel mutation of the VEGF promoter was detected in breast cancer cases, and the deletion allele (DD) presented dominant distribution in patients comparing to the insert type (II). Further analysis revealed that the 18-bp deletion eliminated the recognition sites of GA binding protein alpha (GABPα), which was confirmed by binding experiments. Functionally, the GABPα expression is decreased in breast cancer tissues, and acts as a tumor suppressor to inhibit proliferation, migration, invasion and angiogenesis of breast cancer cells, accompanied by accelerated tumor cell apoptosis. In addition, consistent regulatory roles were investigated in mouse models in response to GABPα overexpression or knockdown as well. Mechanistically, we revealed that GABPα inhibited breast cancer progression and angiogenesis by downregulating VEGF transcription via the 18-bp promoter sequences.
conclusionsOur findings provide insights into angiogenic targeted strategy aiming at GABPα-VEGF axis in clinical diagnosis and therapy of breast cancer.
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