Cytosolic serine hydroxymethyltransferase controls lung adenocarcinoma cells migratory ability by modulating AMP kinase activity.

Autor: Bouzidi A; Department of Biochemical Sciences A. Rossi Fanelli, Laboratory Affiliated to Istituto Pasteur Italia, Sapienza University of Rome, Piazzale A. Moro 5, 00185, Rome, Italy., Magnifico MC; Department of Biochemical Sciences A. Rossi Fanelli, Laboratory Affiliated to Istituto Pasteur Italia, Sapienza University of Rome, Piazzale A. Moro 5, 00185, Rome, Italy.; Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari 'Aldo Moro', Via Orabona 4, 70121, Bari, Italy., Paiardini A; Department of Biochemical Sciences A. Rossi Fanelli, Laboratory Affiliated to Istituto Pasteur Italia, Sapienza University of Rome, Piazzale A. Moro 5, 00185, Rome, Italy., Macone A; Department of Biochemical Sciences A. Rossi Fanelli, Laboratory Affiliated to Istituto Pasteur Italia, Sapienza University of Rome, Piazzale A. Moro 5, 00185, Rome, Italy., Boumis G; Department of Biochemical Sciences A. Rossi Fanelli, Laboratory Affiliated to Istituto Pasteur Italia, Sapienza University of Rome, Piazzale A. Moro 5, 00185, Rome, Italy., Giardina G; Department of Biochemical Sciences A. Rossi Fanelli, Laboratory Affiliated to Istituto Pasteur Italia, Sapienza University of Rome, Piazzale A. Moro 5, 00185, Rome, Italy., Rinaldo S; Department of Biochemical Sciences A. Rossi Fanelli, Laboratory Affiliated to Istituto Pasteur Italia, Sapienza University of Rome, Piazzale A. Moro 5, 00185, Rome, Italy., Liberati FR; Department of Biochemical Sciences A. Rossi Fanelli, Laboratory Affiliated to Istituto Pasteur Italia, Sapienza University of Rome, Piazzale A. Moro 5, 00185, Rome, Italy., Lauro C; Department of Physiology and Pharmacology V. Erspamer, Sapienza University of Rome, Piazzale A. Moro 5, 00185, Rome, Italy., Limatola C; Department of Physiology and Pharmacology V. Erspamer, Sapienza University of Rome, Piazzale A. Moro 5, 00185, Rome, Italy., Lanzillotta C; Department of Biochemical Sciences A. Rossi Fanelli, Laboratory Affiliated to Istituto Pasteur Italia, Sapienza University of Rome, Piazzale A. Moro 5, 00185, Rome, Italy., Tramutola A; Department of Biochemical Sciences A. Rossi Fanelli, Laboratory Affiliated to Istituto Pasteur Italia, Sapienza University of Rome, Piazzale A. Moro 5, 00185, Rome, Italy., Perluigi M; Department of Biochemical Sciences A. Rossi Fanelli, Laboratory Affiliated to Istituto Pasteur Italia, Sapienza University of Rome, Piazzale A. Moro 5, 00185, Rome, Italy., Sgarbi G; Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Irnerio 48, 40126, Bologna, Italy., Solaini G; Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Irnerio 48, 40126, Bologna, Italy., Baracca A; Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Irnerio 48, 40126, Bologna, Italy., Paone A; Department of Biochemical Sciences A. Rossi Fanelli, Laboratory Affiliated to Istituto Pasteur Italia, Sapienza University of Rome, Piazzale A. Moro 5, 00185, Rome, Italy. alessio.paone@uniroma1.it., Cutruzzolà F; Department of Biochemical Sciences A. Rossi Fanelli, Laboratory Affiliated to Istituto Pasteur Italia, Sapienza University of Rome, Piazzale A. Moro 5, 00185, Rome, Italy. francesca.cutruzzola@uniroma1.it.
Jazyk: angličtina
Zdroj: Cell death & disease [Cell Death Dis] 2020 Nov 26; Vol. 11 (11), pp. 1012. Date of Electronic Publication: 2020 Nov 26.
DOI: 10.1038/s41419-020-03215-0
Abstrakt: Nutrient utilization and reshaping of metabolism in cancer cells is a well-known driver of malignant transformation. Less clear is the influence of the local microenvironment on metastasis formation and choice of the final organ to invade. Here we show that the level of the amino acid serine in the cytosol affects the migratory properties of lung adenocarcinoma (LUAD) cells. Inhibition of serine or glycine uptake from the extracellular milieu, as well as knockdown of the cytosolic one-carbon metabolism enzyme serine hydroxymethyltransferase (SHMT1), abolishes migration. Using rescue experiments with a brain extracellular extract, and direct measurements, we demonstrate that cytosolic serine starvation controls cell movement by increasing reactive oxygen species formation and decreasing ATP levels, thereby promoting activation of the AMP sensor kinase (AMPK) by phosphorylation. Activation of AMPK induces remodeling of the cytoskeleton and finally controls cell motility. These results highlight that cytosolic serine metabolism plays a key role in controlling motility, suggesting that cells are able to dynamically exploit the compartmentalization of this metabolism to adapt their metabolic needs to different cell functions (movement vs. proliferation). We propose a model to explain the relevance of serine/glycine metabolism in the preferential colonization of the brain by LUAD cells and suggest that the inhibition of serine/glycine uptake and/or cytosolic SHMT1 might represent a successful strategy to limit the formation of brain metastasis from primary tumors, a major cause of death in these patients.
Databáze: MEDLINE
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