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

Authors
 Nahee Hwang  ;  Bo Kyung Yoon  ;  Kyu-Hye Chun  ;  Hyeonhui Kim  ;  Yoseob Lee  ;  Jae-Won Kim  ;  Hyeonuk Jeon  ;  Tae-Hyun Kim  ;  Mi-Young Kim  ;  Sungsoon Fang  ;  Jae-Ho Cheong  ;  Jae-Woo Kim 
Citation
 EXPERIMENTAL AND MOLECULAR MEDICINE, Vol.55(11) : 2461-2472, 2023-11 
Journal Title
EXPERIMENTAL AND MOLECULAR MEDICINE
ISSN
 1226-3613 
Issue Date
2023-11
MeSH
Caveolin 1* / genetics ; Caveolin 1* / metabolism ; Down-Regulation ; Endocytosis ; Humans ; Stomach Neoplasms* / genetics ; Stomach Neoplasms* / metabolism
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, successfully blocked caveolin-1-mediated endocytosis, leading to the marked suppression of tumor growth in chemorefractory 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.
Files in This Item:
T202306773.pdf Download
DOI
10.1038/s12276-023-01109-7
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Mi Young(김미영)
Kim, Jae Woo(김재우) ORCID logo https://orcid.org/0000-0001-5456-9495
Kim, Tae Hyun(김태현)
Yoon, Bo Kyung(윤보경)
Cheong, Jae Ho(정재호) ORCID logo https://orcid.org/0000-0002-1703-1781
Fang, Sungsoon(황성순) ORCID logo https://orcid.org/0000-0003-0201-5567
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/197328
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