mTOR-driven integrin β4-enriched extracellular vesicles from lenvatinib-resistant hepatocellular carcinoma fuel lung metastasis via fibroblast-niche formation - PubMed
5 hours ago
- #Lung Metastasis
- #Extracellular Vesicles
- #Hepatocellular Carcinoma
- Lenvatinib-resistant (LR) hepatocellular carcinoma (HCC) cells release more extracellular vesicles (EVs), enhancing lung metastasis.
- mTOR signaling activation in LR cells increases EV secretion by blocking autophagic degradation of multivesicular bodies.
- LR-derived EVs are enriched with integrin β4 (ITGβ4), promoting pre-metastatic niche formation via ITGβ4-laminin interaction and PI3K-AKT-p65 pathway in lung fibroblasts.
- High plasma EV-ITGβ4 levels in LR HCC patients correlate with poor prognosis.
- Rapamycin inhibits mTOR, reducing lung metastasis and restoring lenvatinib sensitivity.