2026-04-04T02:39:28Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1176302025-12-04T21:16:01Zcom_2072_1057col_2072_478781col_2072_478917

00925njm 22002777a 4500 dc Pey, Jon author San José-Eneriz, Edurne author Ochoa, María Carmen author Apaolaza, Iñigo author Atauri, Pedro de author Rubio, Angel author Cendoya, Xabier author Miranda, Estíbaliz author Garate, Leire author Cascante i Serratosa, Marta author Carracedo, Arkaitz author Agirre, Xabier author Prosper, Felipe author Planes, Francisco J. author 2017-11-10T14:53:07Z 2017-11-10T14:53:07Z 2017-10-30 2017-11-10T14:53:07Z 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 Poliamines Càncer Enzims Polyamines Cancer Enzymes In-silico gene essentiality analysis of polyamine biosynthesis reveals APRT as a potential target in cancer