Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Sep;13(17):2585-96.
doi: 10.1002/pmic.201200298. Epub 2013 Jul 30.

Oncogene-induced cellular senescence elicits an anti-Warburg effect

Mingxi Li  1 , Kenneth R Durbin, Steve M M Sweet, Jeremiah D Tipton, Yupeng Zheng, Neil L Kelleher
Affiliations

Oncogene-induced cellular senescence elicits an anti-Warburg effect

Mingxi Li et al. Proteomics. 2013 Sep.

Abstract

Cellular senescence, an irreversible cell cycle arrest induced by a diversity of stimuli, has been considered as an innate tumor suppressing mechanism with implications and applications in cancer therapy. Using a targeted proteomics approach, we show that fibroblasts induced into senescence by expression of oncogenic Ras exhibit a decrease of global acetylation on all core histones, consistent with formation of senescence-associated heterochromatic foci. We also detected clear increases in repressive markers (e.g. >50% elevation of H3K27me2/3) along with decreases in histone marks associated with increased transcriptional expression/elongation (e.g. H3K36me2/3). Despite the increases in repressive marks of chromatin, 179 loci (of 2206 total) were found to be upregulated by global quantitative proteomics. The changes in the cytosolic proteome indicated an upregulation of mitochondrial proteins and downregulation of proteins involved in glycolysis. These alterations in primary metabolism are opposite to the well-known Warburg effect observed in cancer cells. This study significantly improves our understanding of stress-induced senescence and provides a potential application for triggering it in antiproliferative strategies that target the primary metabolism in cancer cells.

Keywords: Cell biology; Histones; Metabolism; Oxidative phosphorylation; Senescence.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Figure 2
Figure 2
Figure 3
Figure 3
Figure 4
Figure 4
Figure 5
Figure 5
Figure 6
Figure 6
Figure 7
Figure 7
See this image and copyright information in PMC

Comment in

References

    1. Lowe SW, Cepero E, Evan G. Intrinsic tumour suppression. Nature. 2004;432:307–315. - PubMed
    1. Hayflick L. LIMITED IN VITRO LIFETIME OF HUMAN DIPLOID CELL STRAINS. Experimental Cell Research. 1965;37:614. - PubMed
    1. Wright WE, Shay JW. Telomere dynamics in cancer progression and prevention: fundamental differences in human and mouse telomere biology. Nature Medicine. 2000;6:849–851. - PubMed
    1. Chiantore MV, Vannucchi S, Mangino G, Percario ZA, et al. Senescence and Cell Death Pathways and Their Role in Cancer Therapeutic Outcome. Current Medicinal Chemistry. 2009;16:287–300. - PubMed
    1. Shay JW, Roninson IB. Hallmarks of senescence in carcinogenesis and cancer therapy. Oncogene. 2004;23:2919–2933. - PubMed

Publication types

MeSH terms