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A Multi-omics PTM Atlas Reveals Key Insights into Metabolic Reprogramming in Colorectal Cancer.

Tianyuan Li1, Jingjing Dong2, Yujie Zhang1

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Cancer Genomics & Proteomics
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PubMed
Summary

Post-translational modifications (PTMs) like phosphorylation, ubiquitination, and malonylation significantly alter colorectal cancer (CRC) metabolism by affecting key enzymes. These PTMs offer potential therapeutic targets for CRC treatment.

Keywords:
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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Colorectal cancer (CRC) is a major cause of cancer mortality globally.
  • Metabolic reprogramming is a key hallmark of cancer.
  • The role of post-translational modifications (PTMs) in CRC metabolic reprogramming is not well understood.

Purpose of the Study:

  • To investigate the contribution of phosphorylation, ubiquitination, and malonylation to metabolic reprogramming in colorectal cancer.
  • To identify key metabolic enzymes and regulatory sites affected by PTMs in CRC.
  • To explore the PTM-regulated metabolic network in CRC.

Main Methods:

  • Analysis of phosphorylation, ubiquitination, and malonylation in paired CRC and adjacent normal tissues using high-resolution mass spectrometry.
  • Identification of differential PTM patterns, key regulatory enzymes, and modification sites.
  • Functional enrichment, protein-protein interaction (PPI) network analysis, and multi-omics integration.

Main Results:

  • Identified significant differential PTMs, including 59 phosphorylation, 263 ubiquitination, and 64 malonylation sites in CRC tissues.
  • Observed PTMs affecting key metabolic enzymes such as IDH1, LDHA, PDHA1, and GAPDH.
  • Revealed a PTM-regulated metabolic network, suggesting PTMs' role in CRC metabolic reprogramming and altered glycolysis.

Conclusions:

  • Post-translational modifications (PTMs) contribute to metabolic reprogramming in colorectal cancer by modulating key metabolic enzymes.
  • PTM-regulated pathways involving enzymes like IDH1, LDHA, PDHA1, and GAPDH influence glycolysis and energy metabolism in CRC.
  • PTM-regulated pathways represent potential therapeutic targets for colorectal cancer, with the PTM atlas providing insights into CRC's metabolic landscape.