Heterogeneity of tumor-induced gene expression changes in the human metabolic network

Jie Hu1, Jason W Locasale, Jason H Bielas

  • 1Center for Computational Biology and Bioinformatics and Initiative in Systems Biology, Columbia University, New York, New York, USA.

Nature Biotechnology
|April 23, 2013
PubMed

Insights

Cancer cells reprogram metabolism, but gene expression largely mirrors normal tissues. Some pathways like glycolysis change universally, while others vary, offering potential therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Cellular metabolism reprogramming is a key feature of cancer.
  • Understanding metabolic gene expression differences between tumors and normal tissues is crucial.

Purpose of the Study:

  • To compare metabolic gene expression patterns across diverse human tumor types.
  • To identify common and heterogeneous metabolic alterations in cancer.
  • To explore potential therapeutic targets based on metabolic gene expression.

Main Methods:

  • Comparative analysis of metabolic gene expression profiles.
  • Examination across 22 distinct human tumor types.
  • Investigation of individual biochemical reactions and isoenzymes.

Main Results:

  • Tumor metabolic gene expression largely resembles that of corresponding normal tissues.
  • Upregulation of nucleotide biosynthesis and glycolysis is common across tumors.
  • Oxidative phosphorylation exhibits heterogeneous expression changes.
  • Metabolic gene expression changes can mimic or enhance tumor-driving mutations.
  • Hundreds of metabolic isoenzymes show significant, tumor-specific expression changes.

Conclusions:

  • While some metabolic pathways are consistently altered in cancer, significant heterogeneity exists.
  • Tumor-specific expression changes in metabolic isoenzymes represent promising targets for novel anticancer therapies.

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