Role of EMT in the DNA damage response, double-strand break repair pathway choice and its implications in cancer treatment

Cancer Sci. 2022 Jul;113(7):2214-2223. doi: 10.1111/cas.15389. Epub 2022 May 24.

Abstract

Numerous epithelial-mesenchymal transition (EMT) characteristics have now been demonstrated to participate in tumor development. Indeed, EMT is involved in invasion, acquisition of stem cell properties, and therapy-associated resistance of cancer cells. Together, these mechanisms offer advantages in adapting to changes in the tumor microenvironment. However, recent findings have shown that EMT-associated transcription factors (EMT-TFs) may also be involved in DNA repair. A better understanding of the coordination between the DNA repair pathways and the role played by some EMT-TFs in the DNA damage response (DDR) should pave the way for new treatments targeting tumor-specific molecular vulnerabilities, which result in selective destruction of cancer cells. Here we review recent advances, providing novel insights into the role of EMT in the DDR and repair pathways, with a particular focus on the influence of EMT on cellular sensitivity to damage, as well as the implications of these relationships for improving the efficacy of cancer treatments.

Keywords: DNA damage response; DNA repair; ZEB1; epithelial-mesenchymal transition; synthetic lethality.

Publication types

  • Review

MeSH terms

  • DNA Damage / genetics
  • DNA Repair / genetics
  • Epithelial-Mesenchymal Transition* / genetics
  • Humans
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • Transcription Factors / genetics
  • Tumor Microenvironment / genetics

Substances

  • Transcription Factors