Metabolite systems profiling identifies exploitable weaknesses in retinoblastoma

FEBS Lett. 2019 Jan;593(1):23-41. doi: 10.1002/1873-3468.13294. Epub 2018 Nov 27.

Abstract

Retinoblastoma (RB) is a childhood eye cancer. Currently, chemotherapy, local therapy, and enucleation are the main ways in which these tumors are managed. The present work is the first study that uses constraint-based reconstruction and analysis approaches to identify and explain RB-specific survival strategies, which are RB tumor specific. Importantly, our model-specific secretion profile is also found in RB1-depleted human retinal cells in vitro and suggests that novel biomarkers involved in lipid metabolism may be important. Finally, RB-specific synthetic lethals have been predicted as lipid and nucleoside transport proteins that can aid in novel drug target development.

Keywords: cancer metabolism; constraint-based reconstruction and modeling; retinoblastoma; synthetic lethal; systems biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport
  • Biomarkers, Tumor / metabolism
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Disease Progression
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lipid Metabolism
  • Metabolomics / methods*
  • Models, Theoretical
  • Nucleosides / metabolism
  • Retinoblastoma / genetics*
  • Retinoblastoma / metabolism
  • Retinoblastoma Binding Proteins / genetics*
  • Sequence Analysis, RNA / methods*
  • Synthetic Lethal Mutations
  • Systems Biology / methods*
  • Ubiquitin-Protein Ligases / genetics*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Nucleosides
  • RB1 protein, human
  • Retinoblastoma Binding Proteins
  • Ubiquitin-Protein Ligases