Caveolin-1 mediates the utilization of extracellular proteins for survival in refractory gastric cancer.

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 chemoresistant gastric cancer cells rely heavily on endocytosis, facilitated by caveolin-1, for survival. caveolin-1 was highly upregulated in the most malignant stem-like/EMT/mesenchymal (SEM)-type gastric cancer cells, allowing caveolin-1-mediated endocytosis and utilization of extracellular proteins via lysosomal degradation. Downregulation 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, a lysosomal inhibitor, s

SUBMITTER: Hwang N 

PROVIDER: S-EPMC10689497 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature