Cell Signaling Pathways Related to Epithelial Mesenchymal Transition in Cancer Metastasis

Crit Rev Oncog. 2019;24(1):47-54. doi: 10.1615/CritRevOncog.2018029509.

Abstract

The epithelial mesenchymal transition (EMT) is a highly complex and dynamic morphogenetic process in which epithelial cells change their cellular characteristics and transform to mesenchymal cells. It plays a key role in tissue remodeling, not only during embryonic development and stem cell biology but also during wound healing, fibrosis, and cancer progression. In EMT, under different extracellular cell signals and stimuli, epithelial cells undergo an orchestrated series of morphological, cellular, biochemical, and molecular changes. The mechanism of cancer cell metastasis is similar to embryonic development, like epithelial cells migrating and differentiating into all tissues of the embryo. In this period, epithelial cells differentiate into mesenchymal cells, migrate, and return to the epithelial cells when necessary. The important cell signaling pathways in embryonic development, such as growth factor receptor tyrosine kinases (FGF, HGF, TGF-α), TGF-β, Wnt, NOTCH, MAPK, JAK/STAT and inflammatory cytokines such as NF-κB, TNF-α, IL6, cathepsin and HIF-1α. All play crucial roles in EMT during cancer cell invasion and metastasis. In cancer progression, similar cell signaling pathways and molecular activation occur in embryonic development; therefore, it is important to understand the molecular mechanisms of cell signaling pathways related to cancer metastasis and improve new diagnostic and therapeutic approaches for resistance to drugs.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers
  • Cell Movement
  • Epithelial-Mesenchymal Transition*
  • Extracellular Space / metabolism
  • Gene Expression Regulation
  • Humans
  • Neoplasm Metastasis
  • Neoplasms / etiology
  • Neoplasms / metabolism*
  • Neoplasms / pathology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / metabolism
  • Transcription Factors / metabolism
  • Transforming Growth Factor beta / metabolism
  • Wnt Signaling Pathway

Substances

  • Biomarkers
  • Transcription Factors
  • Transforming Growth Factor beta
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases