Proteomic and Metabolomic Characterization of a Mammalian Cellular Transition from Quiescence to Proliferation

Abstract

There exist similarities and differences in metabolism and physiology between normal proliferative cells and tumor cells. Once a cell enters the cell cycle, metabolic machinery is engaged to facilitate various processes. The kinetics and regulation of these metabolic changes have not been properly evaluated. To correlate the orchestration of these processes with the cell cycle, we analyzed the transition from quiescence to proliferation of a non-malignant murine pro-B lymphocyte cell line in response to IL-3. Using multiplex mass-spectrometry-based proteomics we show that the transition to proliferation shares features generally attributed to cancer cells: up-regulation of glycolysis, lipid metabolism, amino-acid synthesis, and nucleotide synthesis and down-regulation of oxidative phosphorylation and the urea cycle. Furthermore, metabolomic profiling of this transition reveals similarities to cancer-related metabolic pathways. In particular, we find that methionine is consumed at a higher rate than other essential amino acids, with a potential link to epigenetic maintenance.