APOA2-mediated endothelial mesenchymal transition and cancer lipid metabolism reprogramming confers antiangiogenic drug resistance through TGF-β - PubMed
5 hours ago
- #TGF-β
- #Angiogenesis
- #Hepatocellular Carcinoma
- APOA2 mediates endothelial-to-mesenchymal transition (EndoMT) and reprograms cancer lipid metabolism, leading to antiangiogenic drug (AAD) resistance in hepatocellular carcinoma (HCC).
- APOA2 overexpression in HCC reduces VEGFR2 expression in vascular endothelial cells, promoting cancer cell proliferation and reducing apoptosis.
- Transcriptome sequencing of human HCC specimens showed higher APOA2 expression in AAD-resistant cases.
- APOA2 overexpression in an HCC mouse model confirmed resistance to AAD therapy, with no effect on tumor angiogenesis but increased cancer cell proliferation and reduced apoptosis.
- Proteomic analysis revealed APOA2 upregulates TGF-β-related proteins, increasing TGF-β secretion in HCC cells and mouse models.
- TGF-β reduces VEGFR2 expression, induces mesenchymal gene expression in endothelial cells, and initiates fatty acid oxidation metabolic reprogramming in cancer cells.
- Inhibition of TGF-β reverses APOA2-mediated EndoMT and lipid metabolism reprogramming, reducing angiogenesis and tumor proliferation.
- High APOA2-expressing HCC relies on TGF-β for proliferation and angiogenesis, suggesting TGF-β inhibition as a potential therapeutic strategy.