Molecular mechanisms of epithelial to mesenchymal transition in tumor metastasis

Acta Biochim Pol. 2019 Dec 28;66(4):509-520. doi: 10.18388/abp.2019_2899.

Abstract

Epithelial to mesenchymal transition (EMT) is a process during which cancer cells lose epithelial features, cytoskeletal architecture is re-organized, cell shape changes and cells activate genes that help to define mesenchymal phenotype, what leads to an increased cell motility and dissemination of tumor to distant metastatic sites. This review describes different signaling networks between microRNAs and proteins that regulate EMT in tumor growth. Activation of EMT is mediated via series of paracrine signaling molecules. WNT, TGF-b, NOTCH and Shh signaling pathways play crucial roles in activation of EMT-related transcription factors, such as SNAIL, SLUG, ZEB1/2 or TWIST. Recent data provide evidence that crosstalk between microRNAs, long non-coding RNAs and EMT-transcription factors is crucial event in EMT regulation. MicroRNAs affect also level of proteins responsible for cellular contact, adhesion and cytoskeletal proteins, what induces changes of epithelial to mesenchymal phenotype. Understanding of those signaling networks may help to identify novel biomarkers or develop new treatment strategies based on microRNA therapeutics in future.

Publication types

  • Review

MeSH terms

  • Cell Movement / genetics*
  • Epithelial-Mesenchymal Transition / genetics*
  • Hedgehog Proteins / genetics
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Metastasis
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Receptors, Notch / genetics
  • Snail Family Transcription Factors / genetics
  • Transforming Growth Factor beta / genetics
  • Twist-Related Protein 1 / genetics
  • Wnt Signaling Pathway / genetics
  • Zinc Finger E-box-Binding Homeobox 1 / genetics

Substances

  • Hedgehog Proteins
  • MicroRNAs
  • Receptors, Notch
  • SHH protein, human
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • Transforming Growth Factor beta
  • Twist-Related Protein 1
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1