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- W4379389611 abstract "Abstract Despite advances in cancer therapy, the clinical outcome of patients with gastric cancer remains poor largely due to tumor heterogeneity. Thus, finding a hidden vulnerability of clinically refractory subtypes of gastric cancer is crucial. Here, we report that chemo-resistant gastric cancer cells heavily rely on endocytosis, facilitated by caveolin-1, for survival. caveolin-1 was highly up-regulated in the most malignant SEM (stem-like, EMT, and mesenchymal)-type gastric cancer cells, allowing caveolin-1-mediated endocytosis and utilization of extracellular proteins via lysosomal degradation. Down-regulation of caveolin-1 alone was sufficient to induce cell death in SEM-type gastric cancer cells, emphasizing its importance as a survival mechanism. Consistently, chloroquine, the lysosomal inhibitor, successfully blocked caveolin-1-mediated endocytosis, leading to the marked suppression of tumor growth in chemo-refractory gastric cancer cells in vitro including patient-derived organoids, and in vivo. Together, our findings suggest that caveolin-1-mediated endocytosis is a key metabolic pathway for gastric cancer survival and a potential therapeutic target." @default.
- W4379389611 created "2023-06-06" @default.
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- W4379389611 date "2023-06-05" @default.
- W4379389611 modified "2023-10-01" @default.
- W4379389611 title "Caveolin-1 mediates the utilization of extracellular proteins for survival in refractory gastric cancer" @default.
- W4379389611 doi "https://doi.org/10.21203/rs.3.rs-2878247/v1" @default.
- W4379389611 hasPublicationYear "2023" @default.
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