Fructose-induced mTORC1 Activation Promotes Pancreatic Cancer Progression through Inhibition of Autophagy

In this study, we investigated the functional association between fructose utilization and pancreatic ductal adenocarcinoma (PDAC) progression. Fructose could be taken up and metabolized by PDAC cells and provided an adaptive survival mechanism for PDAC cells under glucose deficient conditions. GLUT5-mediated fructose metabolism maintained the survival, proliferation, and invasion capacities of PDAC cells in vivo and in vitro. Fructose metabolism not only provided ATP and biomass to PDAC cells but also conferred metabolic plasticity to the cells, making them more adaptable to the tumor microenvironment. Mechanistically, fructose activated AMPK-mTORC1 signaling pathway to inhibit glucose deficiency-induced autophagic cell death. Moreover, the fructose specific transporter GLUT5 was highly expressed in PDAC tissues and was an independent marker of disease progression in PDAC patients. These findings provide mechanistic insights into the role of fructose in promoting PDAC progression and offer potential strategies for targeting metabolism to treat PDAC.PMID:37738413 | DOI:10.1158/0008-5472.CAN-23-0464

Source: Cell Research - September 22, 2023 Category: Cytology Authors: Yanfen Cui Jianfei Tian Zhaosong Wang Hui Guo He Zhang Zhiyong Wang Hui Liu Weijie Song Liming Liu Ruinan Tian Xiaoyan Zuo Sixin Ren Ruifang Niu Fei Zhang Source Type: research