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- W2891882242 abstract "e15741 Background: Aerobic glycolysis, regulated by mammalian target of rapamycin (mTOR) pathway, plays an important role in pancreatic carcinogenesis. Regulated in development and DNA damage response (Redd1) constitutes an important regulator of mTOR signaling. Previously, we observed that the loss of heterozygosity (LOH) status of Kras mutations (e.g. KrasG12D) is associated with an increased Redd1 expression. Here, we investigated the functional relevance of Redd1 in the context of KrasG12D-LOH. Methods: Murine Kras G12D -LOH/Kras G12D pancreatic cancer cells isolated from genetically engineered mice were used in this study. The glycolysis dependence was detected by CCK8 assays after treated by glycolysis inhibitor 2-Deoxy-D-glucose (2-DG). Redd1 expression was down-regulated using shRNA transfection. Cell proliferation was determined by CCK8 and colony formation assays. Cell invasion and migration was measured by transwell and wound-healing assays. The levels of lactic acid and ATP were tested by ELISA kit. Genes related to glycolysis and mTOR signal were evaluated by western-blot and quantitative RT-PCR. Results: Compared with KRAS G12D pancreatic cancer cells, the viability of KRAS G12D -LOH cells decreased significantly in the presence of 2-DG. After Redd1 suppression, the proliferative and invasive potentials of KRAS G12D -LOH cells decreased significantly when compared with blank group and negative group. The levels of lactic acid and ATP were also reduced by Redd1 down-regulation. Furthermore, the signal activity of mTOR pathway and Pkm2 and Hk2 expression were reduced dramatically, while Tsc1 and Tsc2 expression were unaffected. Conclusions: The LOH status of KRAS G12D renders the pancreatic cancer cells additive to glycolysis, which further affect the proliferative and invasive potentials via the function of Redd1/mTOR. These data underscore the importance of KRAS G12D -LOH in regulating cancer glucose metabolism." @default.
- W2891882242 created "2018-09-27" @default.
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- W2891882242 date "2017-05-20" @default.
- W2891882242 modified "2023-10-16" @default.
- W2891882242 title "Effect of Redd1 loss on proliferation and metastasis of pancreatic cancer cells with KrasG12D-LOH by inhibiting glycolysis." @default.
- W2891882242 doi "https://doi.org/10.1200/jco.2017.35.15_suppl.e15741" @default.
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