Methionine restriction and cancer treatment: a systems biology study of yeast to investigate the possible key players.

ABSTRACT

Background/aim: Dietary restriction, mainly carbon and/or methionine restriction are among the upcoming supporting interventions along with chemotherapy in various cancers. Although dietary restriction has been proven to be beneficial, the main cellular machineries affected by its administration lacks deeper information considerably, a notable pitfall in its use as a personalized nutritional approach. Materials and methods: In this study, cellular effects of methionine restriction on a yeast model are explored via systems biology approaches. The methionine biosynthesis network, constructed by integrating interaction data with gene ontology terms, was analysed topologically, and proved to be informative about the intertwined relationship of methionine biosynthesis and cancer. Experimentally, effects of methionine restriction on the yeast model were explored in vivo, with transcriptome analyses. Results: The integrative analysis of the transcriptional data together with the reconstructed network gave insight into cellular machineries such as TOR, MAPK, and sphingolipid-mediated signaling cascades as the mostly responsive cellular pathways in the methionine-restricted cases with Sch9p (functional orthologue of mammalian S6 kinase) being placed at the intersection of these signaling routes.