한빛사논문
- 조회1,091
Nahee Hwang 1,2,3,8, Bo Kyung Yoon 1,3,8, Kyu-Hye Chun 1,2,3, Hyeonhui Kim 2,4, Yoseob Lee 1,2,3, Jae-Won Kim 1,2,3, Hyeonuk Jeon 1,2,3, Tae-Hyun Kim 1,3, Mi-Young Kim 1,3, Sungsoon Fang 2,3,4,*, Jae-Ho Cheong 2,3,5,6,7,* and Jae-woo Kim 1,3,*
1Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Republic of Korea.
2Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea.
3Chronic Intractable Disease for Systems Medicine Research Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
4Severance Biomedical Science Institute, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
5Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
6Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea.
7Department of R&D, Veraverse Inc., Seoul, Republic of Korea.
8These authors contributed equally: Nahee Hwang, Bo Kyung Yoon.
*Corresponding authors: correspondence to Sungsoon Fang, Jae-Ho Cheong or Jae-woo Kim
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.
논문정보
- Research article
- 2023년 11월 (BRIC 등록일 2023-11-03)
- 국내 연구진
- 의약학 > 분자세포의학
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
연구자 ID
관련분야 연구자보기
관련분야 논문보기
