Phospholipid dynamics in ex vivo lung cancer and normal lung explants

Lesko Julia; Triebl Alexander; Stacher-Priehse Elvira; Fink-Neuböck Nicole; Lindenmann Jörg; Smolle-Jüttner Freyja-Maria; Köfeler Harald C.; Hrzenjak Andelko; Olschewski Horst; Leithner Katharina

doi:10.1038/s12276-020-00547-x

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자료유형: 학술저널

저자정보: Lesko Julia (Medical University of Graz) Triebl Alexander (Medical University of Graz) Stacher-Priehse Elvira (Medical University of Graz) Fink-Neuböck Nicole (Medical University of Graz) Lindenmann Jörg (Medical University of Graz) Smolle-Jüttner Freyja-Maria (Medical University of Graz) Köfeler Harald C. (Medical University of Graz) Hrzenjak Andelko (Medical University of Graz) Olschewski Horst (Medical University of Graz) Leithner Katharina (Medical University of Graz)

저널정보: 대한생화학·분자생물학회 Experimental and Molecular Medicine Experimental and Molecular Medicine 제53권

발행연도: 2021.1

수록면: 1 - 10 (10page)

DOI: 10.1038/s12276-020-00547-x

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In cancer cells, metabolic pathways are reprogrammed to promote cell proliferation and growth. While the rewiring of central biosynthetic pathways is being extensively studied, the dynamics of phospholipids in cancer cells are still poorly understood. In our study, we sought to evaluate de novo biosynthesis of glycerophospholipids (GPLs) in ex vivo lung cancer explants and corresponding normal lung tissue from six patients by utilizing a stable isotopic labeling approach. Incorporation of fully 13 C-labeled glucose into the backbone of phosphatidylethanolamine (PE), phosphatidylcholine (PC), and phosphatidylinositol (PI) was analyzed by liquid chromatography/mass spectrometry. Lung cancer tissue showed significantly elevated isotopic enrichment within the glycerol backbone of PE, normalized to its incorporation into PI, compared to that in normal lung tissue; however, the size of the PE pool normalized to the size of the PI pool was smaller in tumor tissue. These findings indicate enhanced PE turnover in lung cancer tissue. Elevated biosynthesis of PE in lung cancer tissue was supported by enhanced expression of the PE biosynthesis genes ETNK2 and EPT1 and decreased expression of the PC and PI biosynthesis genes CHPT1 and CDS2 , respectively, in different subtypes of lung cancer in publicly available datasets. Our study demonstrates that incorporation of glucose-derived carbons into the glycerol backbone of GPLs can be monitored to study phospholipid dynamics in tumor explants and shows that PE turnover is elevated in lung cancer tissue compared to normal lung tissue.

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