Radiation induces senescence and a bystander effect through metabolic alterations.

E. C. Liao, Y. T. Hsu, Q. Y. Chuah, Y. J. Lee, J. Y. Hu, T. C. Huang, P. M. Yang, S. J. Chiu

Research output: Contribution to journalArticle

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Abstract

Cellular senescence is a state of irreversible growth arrest; however, the metabolic processes of senescent cells remain active. Our previous studies have shown that radiation induces senescence of human breast cancer cells that display low expression of securin, a protein involved in control of the metaphase-anaphase transition and anaphase onset. In this study, the protein expression profile of senescent cells was resolved by two-dimensional gel electrophoresis to investigate associated metabolic alterations. We found that radiation induced the expression and activation of glyceraldehyde-3-phosphate dehydrogenase that has an important role in glycolysis. The activity of lactate dehydrogenase A, which is involved in the conversion of pyruvate to lactate, the release of lactate and the acidification of the extracellular environment, was also induced. Inhibition of glycolysis by dichloroacetate attenuated radiation-induced senescence. In addition, radiation also induced activation of the 5'-adenosine monophosphate-activated protein kinase (AMPK) and nuclear factor kappa B (NF-κB) pathways to promote senescence. We also found that radiation increased the expression of monocarboxylate transporter 1 (MCT1) that facilitates the export of lactate into the extracellular environment. Inhibition of glycolysis or the AMPK/NF-κB signalling pathways reduced MCT1 expression and rescued the acidification of the extracellular environment. Interestingly, these metabolic-altering signalling pathways were also involved in radiation-induced invasion of the surrounding, non-irradiated breast cancer and normal endothelial cells. Taken together, radiation can induce the senescence of human breast cancer cells through metabolic alterations.

Original languageEnglish
JournalCell Death and Disease
Volume5
DOIs
Publication statusPublished - 2014

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Bystander Effect
Radiation
Glycolysis
Lactic Acid
Anaphase
NF-kappa B
Adenosine Monophosphate
Breast Neoplasms
Protein Kinases
Securin
Glyceraldehyde-3-Phosphate Dehydrogenases
Cell Aging
Electrophoresis, Gel, Two-Dimensional
Metaphase
Pyruvic Acid
Proteins
Endothelial Cells
Growth

ASJC Scopus subject areas

  • Medicine(all)

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Radiation induces senescence and a bystander effect through metabolic alterations. / Liao, E. C.; Hsu, Y. T.; Chuah, Q. Y.; Lee, Y. J.; Hu, J. Y.; Huang, T. C.; Yang, P. M.; Chiu, S. J.

In: Cell Death and Disease, Vol. 5, 2014.

Research output: Contribution to journalArticle

Liao, E. C. ; Hsu, Y. T. ; Chuah, Q. Y. ; Lee, Y. J. ; Hu, J. Y. ; Huang, T. C. ; Yang, P. M. ; Chiu, S. J. / Radiation induces senescence and a bystander effect through metabolic alterations. In: Cell Death and Disease. 2014 ; Vol. 5.
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