Metabolic reprogramming and epithelial-to-mesenchymal transition in cancer

FEBS J. 2017 Oct;284(19):3132-3144. doi: 10.1111/febs.14090. Epub 2017 May 21.

Abstract

Several lines of evidence indicate that during transformation epithelial cancer cells can acquire mesenchymal features via a process called epithelial-to-mesenchymal transition (EMT). This process endows cancer cells with increased invasive and migratory capacity, enabling tumour dissemination and metastasis. EMT is associated with a complex metabolic reprogramming, orchestrated by EMT transcription factors, which support the energy requirements of increased motility and growth in harsh environmental conditions. The discovery that mutations in metabolic genes such as FH, SDH and IDH activate EMT provided further evidence that EMT and metabolism are intertwined. In this review, we discuss the role of EMT in cancer and the underpinning metabolic reprogramming. We also put forward the hypothesis that, by altering chromatin structure and function, metabolic pathways engaged by EMT are necessary for its full activation.

Keywords: EMT; FH; IDH; SDH; cancer; epigenetics; metabolism; metastasis; mitochondrial metabolism.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Movement
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism*
  • Cell Transformation, Neoplastic / pathology
  • Cellular Reprogramming / genetics*
  • Chromatin / chemistry
  • Chromatin / metabolism
  • Epithelial-Mesenchymal Transition / genetics*
  • Fumarate Hydratase / genetics
  • Fumarate Hydratase / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Isocitrate Dehydrogenase / metabolism
  • Metabolic Networks and Pathways / genetics*
  • Mutation
  • Neoplasm Invasiveness
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Succinate Dehydrogenase / genetics
  • Succinate Dehydrogenase / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Chromatin
  • Transcription Factors
  • Isocitrate Dehydrogenase
  • Succinate Dehydrogenase
  • Fumarate Hydratase