학술논문
Nutrient scavenging-fueled growth in pancreatic cancer depends on caveolae-mediated endocytosis under nutrient-deprived conditions.
Document Type
Academic Journal
Author
Wolfe AR; Department of Radiation Oncology, The University of Arkansas for Medical Sciences, The Winthrop P. Rockefeller Cancer Institute, Little Rock, AR, USA.; Cui T; Department of Radiation Oncology, City of Hope, Duarte, CA, USA.; Baie S; Department of Cancer Biology and Genetics, The Ohio State University Wexner Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, OH, USA.; Corrales-Guerrero S; Department of Radiation Oncology, City of Hope, Duarte, CA, USA.; Webb A; Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA.; Castro-Aceituno V; Department of Radiation Oncology, City of Hope, Duarte, CA, USA.; Shyu DL; Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, OH, USA.; Karasinska JM; Pancreas Centre BC, Vancouver, BC, Canada.; Topham JT; Pancreas Centre BC, Vancouver, BC, Canada.; Renouf DJ; Pancreas Centre BC, Vancouver, BC, Canada.; Department of Medical Oncology, BC Cancer, Vancouver, BC, Canada.; Schaeffer DF; Pancreas Centre BC, Vancouver, BC, Canada.; Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver, BC, Canada.; Halloran M; Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, OH, USA.; Packard R; Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, OH, USA.; Robb R; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Chen W; Department of Pathology, The Ohio State University Wexner Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, OH, USA.; Denko N; Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, OH, USA.; Lisanti M; Translational Medicine, University of Salford, Greater Manchester M5 4WT, UK.; Lunella Biotech, Inc., 145 Richmond Road, Ottawa, ON K1Z 1A1, Canada.; Thompson TC; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, USA.; Frank P; SGS France, Health & Nutrition, Saint-Benoît, France.; N2C, Nutrition Growth and Cancer, Faculté de Médecine, Université de Tours, Inserm, UMR, 1069 Tours, France.; Williams TM; Department of Radiation Oncology, City of Hope, Duarte, CA, USA.
Source
Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101653440 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2375-2548 (Electronic) Linking ISSN: 23752548 NLM ISO Abbreviation: Sci Adv Subsets: MEDLINE
Subject
Language
English
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is characterized by its nutrient-scavenging ability, crucial for tumor progression. Here, we investigated the roles of caveolae-mediated endocytosis (CME) in PDAC progression. Analysis of patient data across diverse datasets revealed a strong association of high caveolin-1 (Cav-1) expression with higher histologic grade, the most aggressive PDAC molecular subtypes, and worse clinical outcomes. Cav-1 loss markedly promoted longer overall and tumor-free survival in a genetically engineered mouse model. Cav-1-deficient tumor cell lines exhibited significantly reduced proliferation, particularly under low nutrient conditions. Supplementing cells with albumin rescued the growth of Cav-1-proficient PDAC cells, but not in Cav-1-deficient PDAC cells under low glutamine conditions. In addition, Cav-1 depletion led to significant metabolic defects, including decreased glycolytic and mitochondrial metabolism, and downstream protein translation signaling pathways. These findings highlight the crucial role of Cav-1 and CME in fueling pancreatic tumorigenesis, sustaining tumor growth, and promoting survival through nutrient scavenging.