Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/117630
Title: In-silico gene essentiality analysis of polyamine biosynthesis reveals APRT as a potential target in cancer
Author: Pey, J.
San José-Eneriz, E.
Ochoa, M.C.
Apaolaza, I.
Atauri Carulla, Ramón de
Rubio, A.
Cendoya, X.
Miranda, E.
Garate, L.
Cascante, M.
Carracedo, A.
Agirre, X.
Prosper, F.
Planes, F.J.
Keywords: Poliamines
Càncer
Enzims
Polyamines
Cancer
Enzymes
Issue Date: 30-Oct-2017
Publisher: Nature Publishing Group
Abstract: Constraint-based modeling for genome-scale metabolic networks has emerged in the last years as a promising approach to elucidate drug targets in cancer. Beyond the canonical biosynthetic routes to produce biomass, it is of key importance to focus on metabolic routes that sustain the proliferative capacity through the regulation of other biological means in order to improve in-silico gene essentiality analyses. Polyamines are polycations with central roles in cancer cell proliferation, through the regulation of transcription and translation among other things, but are typically neglected in in silico cancer metabolic models. In this study, we analysed essential genes for the biosynthesis of polyamines. Our analysis corroborates the importance of previously known regulators of the pathway, such as Adenosylmethionine Decarboxylase 1 (AMD1) and uncovers novel enzymes predicted to be relevant for polyamine homeostasis. We focused on Adenine phosphoribosyltransferase (APRT) and demonstrated the detrimental consequence of APRT gene silencing on diferent leukaemia cell lines. Our results highlight the importance of revisiting the metabolic models used for in-silico gene essentiality analyses in order to maximize the potential for drug target identifcation in cancer
Note: Reproducció del document publicat a: https://doi.org/10.1038/s41598-017-14067-8
It is part of: Scientific Reports, 2017, vol. 7, p. 14358
Related resource: https://doi.org/10.1038/s41598-017-14067-8
URI: http://hdl.handle.net/2445/117630
ISSN: 2045-2322
Appears in Collections:Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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