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Nuclear reprogramming of cancer stem cells: Corrupting the epigenetic code of cell identity with oncometabolites

Javier A Menendez1, Tomás Alarcón2

  • 1ProCURE (Program Against Cancer Therapeutic Resistance), Metabolism and Cancer Group, Catalan Institute of Oncology, Girona, Catalonia, Spain; Molecular Oncology Group, Girona Biomedical Research Institute (IDIBGI), Salt, Catalonia, Spain.

Molecular & Cellular Oncology
|January 17, 2017
PubMed

Insights

Metabolic changes can corrupt epigenetic codes, driving cancer stem cell (CSC) generation. Oncometabolites enhance reprogramming to CSC states by creating epigenetic resistance to differentiation, highlighting metabolo-epigenetic control in cancer.

Area of Science:

  • Cancer Biology
  • Epigenetics
  • Metabolism

Background:

  • Cancer stem cells (CSCs) are crucial for tumor development and resistance.
  • Epigenetic modifications regulate cell identity and differentiation.
  • Metabolic pathways are increasingly recognized for their role in cancer progression.

Purpose of the Study:

  • To investigate the role of oncometabolites in generating cancer stem cell-like states.
  • To elucidate the mechanisms by which metabolic alterations influence epigenetic reprogramming.
  • To highlight the significance of metabolo-epigenetic communication in cancer.

Main Methods:

  • Utilizing oncometabolites to induce CSC-like states in cells.
  • Assessing epigenetic states and differentiation potential.
  • Analyzing nuclear reprogramming efficiency.
  • Investigating metabolo-epigenetic signaling pathways.

Main Results:

  • Archetypal oncometabolites enhanced the kinetic efficiency of nuclear reprogramming.
  • Cells acquired epigenetic states refractory to differentiation without altering stem cell gene expression.
  • Oncometabolites promoted the generation of CSC-like states *de novo*.
  • Metabolo-epigenetic axes were identified as key drivers.

Conclusions:

  • Metabolic corruption of epigenetic codes is a potential mechanism for CSC generation.
  • Oncometabolites can reprogram cells into CSC-like states by inducing epigenetic resistance.
  • Metabolo-epigenetic interactions are critical for CSC development and maintenance in cancer.
Keywords:
Cancer stem cellsepigeneticsnuclear reprogrammingoncometabolites

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