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Nutrient scavenging-fueled growth in pancreatic cancer depends on caveolae-mediated endocytosis under nutrient-deprived conditions.
Wolfe, Adam R; Cui, Tiantian; Baie, Sooin; Corrales-Guerrero, Sergio; Webb, Amy; Castro-Aceituno, Veronica; Shyu, Duan-Liang; Karasinska, Joanna M; Topham, James T; Renouf, Daniel J; Schaeffer, David F; Halloran, Megan; Packard, Rebecca; Robb, Ryan; Chen, Wei; Denko, Nicholas; Lisanti, Michael; Thompson, Timothy C; Frank, Philippe; Williams, Terence M.
Afiliación
  • 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.
  • Schaeffer DF; Department of Medical Oncology, BC Cancer, Vancouver, BC, Canada.
  • Halloran M; Pancreas Centre BC, Vancouver, BC, Canada.
  • Packard R; Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver, BC, Canada.
  • Robb 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.
  • Chen W; 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.
  • Denko N; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Lisanti M; 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.
  • Thompson TC; 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.
  • Frank P; Translational Medicine, University of Salford, Greater Manchester M5 4WT, UK.
  • Williams TM; Lunella Biotech, Inc., 145 Richmond Road, Ottawa, ON K1Z 1A1, Canada.
Sci Adv ; 10(9): eadj3551, 2024 Mar.
Article en En | MEDLINE | ID: mdl-38427741
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático Límite: Animals / Humans Idioma: En Revista: Sci Adv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático Límite: Animals / Humans Idioma: En Revista: Sci Adv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos