The cytosolic 5’-nucleotidase cN-II lowers the adaptability to glucose deprivation in human breast cancer cells
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Gabriel Bricard1,*, Octavia Cadassou1,*, Laure-Estelle Cassagnes1, Emeline Cros-Perrial1, Léa Payen-Gay1,2, Jean-Yves Puy3, Isabelle Lefebvre-Tournier3, Maria Grazia Tozzi4, Charles Dumontet1 and Lars Petter Jordheim1
1Université De Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, France
2Biochemistry Laboratory of Lyon Sud, Hospices Civils de Lyon, Lyon, France
3IBMM, UMR 5247, CNRS - UM - ENSCM, Université de Montpellier, Montpellier, France
4Department of Biology, Biochemistry Unit, University of Pisa, Pisa, Italy
*These authors have contributed equally to this work
Lars Petter Jordheim, email: [email protected]
Keywords: 5’-nucleotidase, reactive oxygen species, glucose metabolism, hypoxia
Received: March 15, 2017 Accepted: May 22, 2017 Published: June 27, 2017
The cytosolic 5’-nucleotidase cN-II is a highly conserved enzyme implicated in nucleotide metabolism. Based on recent observations suggesting additional roles not directly associated to its enzymatic activity, we studied human cancer cell models with basal or decreased cN-II expression. We developed cancer cells with stable inhibition of cN-II expression by transfection of shRNA-coding plasmids, and studied their biology. We show that human breast cancer cells MDA-MB-231 with decreased cN-II expression better adapt to the disappearance of glucose in growth medium under normoxic conditions than cells with a baseline expression level. This is associated with enhanced in vivo growth and a lower content of ROS in cells cultivated in absence of glucose due to more efficient mechanisms of elimination of ROS. Conversely, cells with low cN-II expression are more sensitive to glucose deprivation in hypoxic conditions. Overall, our results show that cN-II regulates the cellular response to glucose deprivation through a mechanism related to ROS metabolism and defence.
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