Metabolic profiling of cancer cells reveals genome-wide crosstalk between transcriptional regulators and metabolism

Nat Commun. 2019 Apr 23;10(1):1841. doi: 10.1038/s41467-019-09695-9.

Abstract

Transcriptional reprogramming of cellular metabolism is a hallmark of cancer. However, systematic approaches to study the role of transcriptional regulators (TRs) in mediating cancer metabolic rewiring are missing. Here, we chart a genome-scale map of TR-metabolite associations in human cells using a combined computational-experimental framework for large-scale metabolic profiling of adherent cell lines. By integrating intracellular metabolic profiles of 54 cancer cell lines with transcriptomic and proteomic data, we unraveled a large space of associations between TRs and metabolic pathways. We found a global regulatory signature coordinating glucose- and one-carbon metabolism, suggesting that regulation of carbon metabolism in cancer may be more diverse and flexible than previously appreciated. Here, we demonstrate how this TR-metabolite map can serve as a resource to predict TRs potentially responsible for metabolic transformation in patient-derived tumor samples, opening new opportunities in understanding disease etiology, selecting therapeutic treatments and in designing modulators of cancer-related TRs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology*
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic*
  • Genome, Human
  • Humans
  • Metabolic Networks and Pathways
  • Metabolome
  • Metabolomics / methods
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Protein Interaction Mapping
  • Protein Interaction Maps / genetics*
  • Proteomics / methods
  • Transcription Factors / metabolism*
  • Transcriptome

Substances

  • Transcription Factors