Abstract
Cancer cells reprogram their metabolism to meet their demands for survival and proliferation. The metabolic plasticity of tumor cells help them adjust to changes in the availability and utilization of nutrients in the microenvironment. Recent studies revealed that many metabolites and metabolic enzymes have non-metabolic functions contributing to tumorigenesis. One major function is regulating epigenetic modifications to facilitate appropriate responses to environmental cues. Accumulating evidence showed that epigenetic modifications could in turn alter metabolism in tumors. Although a comprehensive understanding of the reciprocal connection between metabolic and epigenetic rewiring in cancer is lacking, some conceptual advances have been made. Understanding the link between metabolism and epigenetic modifications in cancer cells will shed lights on the development of more effective cancer therapies.
Highlights
One hallmark of tumor cells is their rewired metabolism to meet the requirement for macromolecular biosynthesis, survival, and proliferation (Yu and Li, 2017)
We have previously shown that the yeast homolog of PKM2, pyruvate kinase 1 (Pyk1) phosphorylates H3 on threonine 11 (H3T11) and its activity is activated by glucose-derived serine, which in turn represses the transcription of PYK1 (Li et al, 2015; Yu and Li, 2017)
We have previously found that SAM synthetases (Sam1 and Sam2), serine metabolic enzymes (Ser33 and Shm2) and pyruvate kinase Pyk1 form a novel complex called SESAME, which interacts with Set1 methyltransferase complex to promote Set1-catalyzed H3K4 methylation at pyruvate kinase 1 (PYK1) (Li et al, 2015; Yu et al, 2017)
Summary
One hallmark of tumor cells is their rewired metabolism to meet the requirement for macromolecular biosynthesis, survival, and proliferation (Yu and Li, 2017). One important non-metabolic function is regulating epigenetic modifications and gene expression. Epigenetics is defined as heritable changes in gene expression independent of mutations in genomic DNA It originally includes histone post-translational modifications such as acetylation, methylation, ubiquitination, phosphorylation, SUMOylation and DNA modifications. With the development of proteomics and mass spectrometry technology, the repertoire of chromatin modifications is expanding with more epigenetic modifications identified such as acylation (crotonylation, succinylation, propionylation, β-hydroxybutyrylation), O-linked N-acetylglucosamine (O-GlcNAcylation) and RNA modifications (Huang et al, 2014). These modifications play important roles in dictating chromatin structure, regulating gene transcription. The intimate connection between metabolism and epigenetic modifications contributes to tumor initiation and progression
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