Therapeutic implications of cancer epithelial-mesenchymal transition (EMT)

Arch Pharm Res. 2019 Jan;42(1):14-24. doi: 10.1007/s12272-018-01108-7. Epub 2019 Jan 16.

Abstract

The epithelial-mesenchymal transition (EMT) comprises an essential biological process involving cancer progression as well as initiation. While the EMT has been regarded as a phenotypic conversion from epithelial to mesenchymal cells, recent evidence indicates that it plays a critical role in stemness, metabolic reprogramming, immune evasion and therapeutic resistance of cancer cells. Interestingly, several transcriptional repressors including Snail (SNAI1), Slug (SNAI2) and the ZEB family constitute key players for EMT in cancer as well as in the developmental process. Note that the dynamic conversion between EMT and epithelial reversion (mesenchymal-epithelial transition, MET) occurs through variable intermediate-hybrid states rather than being a binary process. Given the close connection between oncogenic signaling and EMT repressors, the EMT has emerged as a therapeutic target or goal (in terms of MET reversion) in cancer therapy. Here we review the critical role of EMT in therapeutic resistance and the importance of EMT as a therapeutic target for human cancer.

Keywords: EMT; Epithelial-mesenchymal transition; Oncogenes; Snail; Therapeutic resistance; Wnt.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / metabolism
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition / drug effects*
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Transcription Factors / antagonists & inhibitors*
  • Transcription Factors / metabolism

Substances

  • Antineoplastic Agents
  • Transcription Factors