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SHR Neuro Krebs Kardio Lipid

Leithner, K; Triebl, A; Trötzmüller, M; Hinteregger, B; Leko, P; Wieser, BI; Grasmann, G; Bertsch, AL; Züllig, T; Stacher, E; Valli, A; Prassl, R; Olschewski, A; Harris, AL; Köfeler, HC; Olschewski, H; Hrzenjak, A.
The glycerol backbone of phospholipids derives from noncarbohydrate precursors in starved lung cancer cells.
Proc Natl Acad Sci U S A. 2018; 115(24):6225-6230 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Grasmann Gabriele Agnes
Hrzenjak Andelko
Köfeler Harald
Leithner Katharina
Leko Petra
Olschewski Andrea
Olschewski Horst
Prassl Ruth
Stacher-Priehse Elvira
Triebl Alexander
Trötzmüller Martin
Wieser Beatrix
Züllig Thomas
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Number of Figures: 5
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Abstract:
Cancer cells are reprogrammed to consume large amounts of glucose to support anabolic biosynthetic pathways. However, blood perfusion and consequently the supply with glucose are frequently inadequate in solid cancers. PEPCK-M (PCK2), the mitochondrial isoform of phosphoenolpyruvate carboxykinase (PEPCK), has been shown by us and others to be functionally expressed and to mediate gluconeogenesis, the reverse pathway of glycolysis, in different cancer cells. Serine and ribose synthesis have been identified as downstream pathways fed by PEPCK in cancer cells. Here, we report that PEPCK-M-dependent glycerol phosphate formation from noncarbohydrate precursors (glyceroneogenesis) occurs in starved lung cancer cells and supports de novo glycerophospholipid synthesis. Using stable isotope-labeled glutamine and lactate, we show that PEPCK-M generates phosphoenolpyruvate and 3-phosphoglycerate, which are at least partially converted to glycerol phosphate and incorporated into glycerophospholipids (GPL) under glucose and serum starvation. This pathway is required to maintain levels of GPL, especially phosphatidylethanolamine (PE), as shown by stable shRNA-mediated silencing of PEPCK-M in H23 lung cancer cells. PEPCK-M shRNA led to reduced colony formation after starvation, and the effect was partially reversed by the addition of dioleyl-PE. Furthermore, PEPCK-M silencing abrogated cancer growth in a lung cancer cell xenograft model. In conclusion, glycerol phosphate formation for de novo GPL synthesis via glyceroneogenesis is a newly characterized anabolic pathway in cancer cells mediated by PEPCK-M under conditions of severe nutrient deprivation. Copyright © 2018 the Author(s). Published by PNAS.
Find related publications in this database (using NLM MeSH Indexing)
A549 Cells -
Animals -
Glucose - metabolism
Glutamine - metabolism
Glycerol - metabolism
Heterografts -
Humans -
Lactic Acid - metabolism
Male -
Mice -
Mice, Nude -
Neoplasms - metabolism
Phosphoenolpyruvate Carboxykinase (ATP) - genetics
Phosphoenolpyruvate Carboxykinase (ATP) - metabolism
Phospholipids - chemistry
Phospholipids - metabolism

Find related publications in this database (Keywords)
cancer
metabolism
glyceroneogenesis
PEPCK
PCK2
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