The histone H3 methyltransferase G9A epigenetically activates the serine-glycine synthesis pathway to sustain cancer cell survival and proliferation

Jane Ding, Tai Li, Xiangwei Wang, Erhu Zhao, Jeong-Hyeon Choi, Liqun Yang, Yunhong Zha, Zheng Dong, Shuang Huang, John M. Asara, Hongjuan Cui, Hanfei Ding

Research output: Contribution to journalArticle

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Abstract

Increased activation of the serine-glycine biosynthetic pathway is an integral part of cancer metabolism that drives macromolecule synthesis needed for cell proliferation. Whether this pathway is under epigenetic control is unknown. Here we show that the histone H3 lysine 9 (H3K9) methyltransferase G9A is required for maintaining the pathway enzyme genes in an active state marked by H3K9 monomethylation and for the transcriptional activation of this pathway in response to serine deprivation. G9A inactivation depletes serine and its downstream metabolites, triggering cell death with autophagy in cancer cell lines of different tissue origins. Higher G9A expression, which is observed in various cancers and is associated with greater mortality in cancer patients, increases serine production and enhances the proliferation and tumorigenicity of cancer cells. These findings identify a G9A-dependent epigenetic program in the control of cancer metabolism, providing a rationale for G9A inhibition as a therapeutic strategy for cancer.

Original languageEnglish (US)
Pages (from-to)896-907
Number of pages12
JournalCell Metabolism
Volume18
Issue number6
DOIs
StatePublished - Dec 3 2013

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Glycine
Serine
Cell Survival
Cell Proliferation
Neoplasms
Epigenomics
Biosynthetic Pathways
Autophagy
Methyltransferases
histone methyltransferase
Histones
Transcriptional Activation
Lysine
Cell Death
Cell Line
Mortality
Enzymes
Genes

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Cite this

The histone H3 methyltransferase G9A epigenetically activates the serine-glycine synthesis pathway to sustain cancer cell survival and proliferation. / Ding, Jane; Li, Tai; Wang, Xiangwei; Zhao, Erhu; Choi, Jeong-Hyeon; Yang, Liqun; Zha, Yunhong; Dong, Zheng; Huang, Shuang; Asara, John M.; Cui, Hongjuan; Ding, Hanfei.

In: Cell Metabolism, Vol. 18, No. 6, 03.12.2013, p. 896-907.

Research output: Contribution to journalArticle

Ding, Jane ; Li, Tai ; Wang, Xiangwei ; Zhao, Erhu ; Choi, Jeong-Hyeon ; Yang, Liqun ; Zha, Yunhong ; Dong, Zheng ; Huang, Shuang ; Asara, John M. ; Cui, Hongjuan ; Ding, Hanfei. / The histone H3 methyltransferase G9A epigenetically activates the serine-glycine synthesis pathway to sustain cancer cell survival and proliferation. In: Cell Metabolism. 2013 ; Vol. 18, No. 6. pp. 896-907.
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