Tumors are currently among the most threatening diseases to human health. One of the most fundatmental feature of malignant tumors is the altered metabolism that provides tumor cells with energy and structural resources necessary for rapid proliferation. In tumor cells, glycolysis pathway is activated, and oxidative phosphorylation is inhibited. Tumor cells usually survive in hypoxia environment, so glycolysis pathway is activated. Tumor cells undergo lower oxygen consumption and faster metabolism, while the intermediate products can supply de novo synthesis of nucleic acid, lipid and amino acid, and the accumulation of lactic acid can reduce pH of tumor microenvironment and promote tumor invasion. All these are advantages of glycolysis pathway.
Chromatin is the intracellular structure that packages DNA in eukaryotic cells. Chromatin can exist in different stable states and is altered by covalent modifications on the histones and the presence of many other factors, such as long non-coding RNAs, protein chaperones. In addition, cellular metabolism also influences chromatin dynamics and epigenetics. The intracellular metabolites that supplied for methylation and acetylation reactions are generally very low, thus limiting the enzymatic activities; however, the chromatin-modifying enzymes, such as DNA methyl-transferase, histone methyltransferase, and histone acetyltransferases, are highly responsive to metabolism altera-tion. Altered glucose and amino acid metabolism in malignant diseases can generate a series substrates used by enzymes that modify chromatin. In tumors, these metabolic changes would lead to abnormal chromatin structure and modification. Furthermore, abnormal tumor metabolism may also affect chromatin related functions such as transcription, gene expression, protein post-translational modification, DNA damage repair etc. Likewise, instable chromatin can cause tumor occurrence or promoted tumor progression. For example, chromatin instability related-gene mutation can cause an altered enzymatic activity resulting in the production of the tumor-promoting metabo-lites. The accumulation of harmful metabolites would further promote tumor progression. A series of common mu-tations in tumors are caused by the accumulation of abnormal metabolites.
With the deepening of the research and the progress of scientific technology, we are becoming increasingly aware of the close relationship between metabolism and chromatin, and the important role of their abnormalities in tumorigenesis and development. It is expected that researchers can use novel technologies such as single-cell or high-throughput analysis to clarify the molecular mechanism of the mutual regulation between metabolism and chromatin and find related new targets for tumor therapy.
This Research Topic aims to discuss the molecular basis of how metabolites influence chromosome modification, chromosome structure, transcription, post-translational modification, DNA damage and repair in tumor. The molecular mechanisms via which chromosomal abnormalities lead to changes in tumor metabolism, such as glucose and lipid metabolism, are also welcome in this topic. We encourage researchers to use single-cell, high-throughput omics and other new technologies to explore molecular mechanisms in tumor cell models, transgenic animals, PDX and other models to explore new targets for tumor therapy.
The topics of interest will comprise of (but will not be limited to) the following:
• Metabolic regulation of chromosome modification
• Metabolic regulation of chromosome structure
• Metabolic regulation of transcription and gene expression
• Metabolic regulation of post-translational modification
• Metabolic regulation of DNA damage and repair
• Epigenetic regulation on glucose metabolism
• Epigenetic regulation on lipid metabolism
Tumors are currently among the most threatening diseases to human health. One of the most fundatmental feature of malignant tumors is the altered metabolism that provides tumor cells with energy and structural resources necessary for rapid proliferation. In tumor cells, glycolysis pathway is activated, and oxidative phosphorylation is inhibited. Tumor cells usually survive in hypoxia environment, so glycolysis pathway is activated. Tumor cells undergo lower oxygen consumption and faster metabolism, while the intermediate products can supply de novo synthesis of nucleic acid, lipid and amino acid, and the accumulation of lactic acid can reduce pH of tumor microenvironment and promote tumor invasion. All these are advantages of glycolysis pathway.
Chromatin is the intracellular structure that packages DNA in eukaryotic cells. Chromatin can exist in different stable states and is altered by covalent modifications on the histones and the presence of many other factors, such as long non-coding RNAs, protein chaperones. In addition, cellular metabolism also influences chromatin dynamics and epigenetics. The intracellular metabolites that supplied for methylation and acetylation reactions are generally very low, thus limiting the enzymatic activities; however, the chromatin-modifying enzymes, such as DNA methyl-transferase, histone methyltransferase, and histone acetyltransferases, are highly responsive to metabolism altera-tion. Altered glucose and amino acid metabolism in malignant diseases can generate a series substrates used by enzymes that modify chromatin. In tumors, these metabolic changes would lead to abnormal chromatin structure and modification. Furthermore, abnormal tumor metabolism may also affect chromatin related functions such as transcription, gene expression, protein post-translational modification, DNA damage repair etc. Likewise, instable chromatin can cause tumor occurrence or promoted tumor progression. For example, chromatin instability related-gene mutation can cause an altered enzymatic activity resulting in the production of the tumor-promoting metabo-lites. The accumulation of harmful metabolites would further promote tumor progression. A series of common mu-tations in tumors are caused by the accumulation of abnormal metabolites.
With the deepening of the research and the progress of scientific technology, we are becoming increasingly aware of the close relationship between metabolism and chromatin, and the important role of their abnormalities in tumorigenesis and development. It is expected that researchers can use novel technologies such as single-cell or high-throughput analysis to clarify the molecular mechanism of the mutual regulation between metabolism and chromatin and find related new targets for tumor therapy.
This Research Topic aims to discuss the molecular basis of how metabolites influence chromosome modification, chromosome structure, transcription, post-translational modification, DNA damage and repair in tumor. The molecular mechanisms via which chromosomal abnormalities lead to changes in tumor metabolism, such as glucose and lipid metabolism, are also welcome in this topic. We encourage researchers to use single-cell, high-throughput omics and other new technologies to explore molecular mechanisms in tumor cell models, transgenic animals, PDX and other models to explore new targets for tumor therapy.
The topics of interest will comprise of (but will not be limited to) the following:
• Metabolic regulation of chromosome modification
• Metabolic regulation of chromosome structure
• Metabolic regulation of transcription and gene expression
• Metabolic regulation of post-translational modification
• Metabolic regulation of DNA damage and repair
• Epigenetic regulation on glucose metabolism
• Epigenetic regulation on lipid metabolism
