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Cell Rep. 2017 Jul 18;20(3):721-736. doi: 10.1016/j.celrep.2017.06.074.

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

Author information

1
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
2
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
3
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
4
Center for Cancer and Cell Biology, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
5
Stem Cell & Regenerative Biology, Genome Institute of Singapore, S138672 Singapore, Singapore.
6
Division of Signal Transduction, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.
7
Division of Gastroenterology, Department of Molecular and Integrative Physiology and Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
8
Meyer Cancer Center, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
9
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: marc@hms.harvard.edu.

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: upregulation of glycolysis, lipid metabolism, amino-acid synthesis, and nucleotide synthesis and downregulation 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 that of other essential amino acids, with a potential link to maintenance of the epigenome.

KEYWORDS:

B cells; IL-3; TMT proteomics; cancer metabolism; cell cycle; cell growth; metabolomics; methionine; protein complexes; quiescence

PMID:
28723573
PMCID:
PMC5626450
DOI:
10.1016/j.celrep.2017.06.074
[Indexed for MEDLINE]
Free PMC Article

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