학술논문
Nutrient scavenging-fueled growth in pancreatic cancer depends on caveolae-mediated endocytosis under nutrient-deprived conditions.
Document Type
Article
Author
Wolfe, Adam R.; Cui, Tiantian; Baie, Sooin; Corrales-Guerrero, Sergio; Webb, Amy; Castro-Aceituno, Veronica; Duan-Liang Shyu; Karasinska, Joanna M.; Topham, James T.; Renouf, Daniel J.; Schaeffer, David F.; Halloran, Megan; Packard, Rebecca; Robb, Ryan; Wei Chen; Denko, Nicholas; Lisanti, Michael; Thompson, Timothy C.; Frank, Philippe; Williams, Terence M.
Source
Subject
*PANCREATIC cancer
*ENDOCYTOSIS
*TUMOR growth
*PANCREATIC duct
*CANCER invasiveness
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Language
ISSN
2375-2548
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. [ABSTRACT FROM AUTHOR]