7.2 Epithelial-mesenchymal transitions

Epithelial-mesenchymal transition (EMT) is a key process in cell migration and morphogenesis. It transforms epithelial cells into mesenchymal cells, enabling them to move and form new structures during development, wound healing, and even cancer spread.

EMT involves losing cell-cell adhesion and gaining motility. This process is controlled by specific genes and signaling pathways, allowing cells to switch between epithelial and mesenchymal states as needed for various biological functions.

Epithelial-Mesenchymal Transition (EMT)

Definition and Developmental Role

Top images from around the web for Definition and Developmental Role

• 

  Frontiers | Epigenetic Regulation of Epithelial to Mesenchymal Transition in the Cancer ... View original

  Is this image relevant?

• 

  Frontiers | Epithelial-Mesenchymal Transition Drives Three-Dimensional Morphogenesis in ... View original

  Is this image relevant?

• 

  Frontiers | Role of Epithelial-Mesenchymal Transition in Retinal Pigment Epithelium Dysfunction View original

  Is this image relevant?

• 

  Frontiers | Epigenetic Regulation of Epithelial to Mesenchymal Transition in the Cancer ... View original

  Is this image relevant?

• 

  Frontiers | Epithelial-Mesenchymal Transition Drives Three-Dimensional Morphogenesis in ... View original

  Is this image relevant?

1 of 3

Top images from around the web for Definition and Developmental Role

• 

  Frontiers | Epigenetic Regulation of Epithelial to Mesenchymal Transition in the Cancer ... View original

  Is this image relevant?

• 

  Frontiers | Epithelial-Mesenchymal Transition Drives Three-Dimensional Morphogenesis in ... View original

  Is this image relevant?

• 

  Frontiers | Role of Epithelial-Mesenchymal Transition in Retinal Pigment Epithelium Dysfunction View original

  Is this image relevant?

• 

  Frontiers | Epigenetic Regulation of Epithelial to Mesenchymal Transition in the Cancer ... View original

  Is this image relevant?

• 

  Frontiers | Epithelial-Mesenchymal Transition Drives Three-Dimensional Morphogenesis in ... View original

  Is this image relevant?

1 of 3

• Epithelial-mesenchymal transition (EMT) transforms polarized epithelial cells into mesenchymal cell phenotype through biochemical changes
• EMT process involves:
  • Loss of cell-cell adhesion
  • Loss of apical-basal polarity
  • Loss of epithelial markers
  • Acquisition of mesenchymal markers
  • Increased cell motility
• Crucial for developmental processes:
  • Gastrulation
  • Neural crest formation
  • Organ development
• Reversible through mesenchymal-epithelial transition (MET) forming secondary epithelia during organogenesis
• Three distinct EMT types:
  • Type 1: Embryonic development and organ formation
  • Type 2: Tissue regeneration and fibrosis
  • Type 3: Cancer progression and metastasis
• Regulated by transcription factor network (Snail, Slug, Twist, Zeb1/2) orchestrating phenotypic changes

EMT in Cellular Processes

• Allows cells to migrate and form new tissues and structures during development
• Facilitates wound healing by promoting cell migration in tissue regeneration
• Enables cancer cells to acquire invasive properties for metastasis
• Confers stem cell-like properties to cancer cells enhancing tumor initiation and therapy resistance
• Contributes to fibrosis when EMT is excessive or prolonged during tissue repair
• Involved in cell reprogramming potentially contributing to induced pluripotent stem cell (iPSC) generation
• Plasticity of EMT/MET transitions helps cancer cells adapt to different microenvironments during metastasis

Molecular Mechanisms of EMT

Transcriptional Regulation

• EMT induction activates specific transcription factors:
  • Snail
  • Slug
  • Twist
  • Zeb1/2
• These factors repress epithelial genes and activate mesenchymal genes
• E-cadherin downregulation leads to:
  • Loss of adherens junctions
  • Decreased cell-cell adhesion
• Upregulation of mesenchymal markers:
  • N-cadherin
  • Vimentin
  • Fibronectin
• Epigenetic modifications regulate EMT-associated gene expression:
  • DNA methylation
  • Histone modifications (acetylation, methylation)

Signaling Pathways

• TGF-β signaling as primary EMT inducer:
  • Activates Smad-dependent pathways
  • Activates Smad-independent pathways
  • Promotes expression of EMT-associated transcription factors
• Wnt signaling contributes to EMT:
  • Acts through β-catenin
  • Cooperates with other pathways
  • Promotes expression of EMT-associated genes
• Notch signaling pathway:
  • Directly activates Snail expression
  • Indirectly supports other EMT-inducing pathways
• Additional pathways involved in EMT regulation:
  • PI3K/AKT pathway
  • MAPK/ERK pathway
  • NF-κB pathway

EMT in Cancer and Regeneration

Cancer Metastasis

• EMT enables epithelial tumor cells to acquire invasive properties
• Facilitates dissemination from primary tumor site to distant organs
• Confers stem cell-like properties to cancer cells:
  • Enhances ability to initiate new tumors (tumor-initiating cells)
  • Increases resistance to therapeutic interventions
• EMT/MET plasticity allows cancer cells to adapt to different microenvironments:
  • Promotes survival during circulation in bloodstream
  • Enables colonization of distant organs
• Understanding EMT in cancer provides potential therapeutic targets:
  • Inhibition of EMT-inducing transcription factors
  • Targeting EMT-associated signaling pathways

Tissue Regeneration

• EMT contributes to wound healing:
  • Promotes cell migration to injury site
  • Enhances production of extracellular matrix components
• Precise regulation of EMT essential for proper tissue repair:
  • Excessive or prolonged EMT can lead to fibrosis (liver cirrhosis, kidney fibrosis)
• EMT involved in cell reprogramming:
  • Contributes to generation of induced pluripotent stem cells (iPSCs)
  • Enhances cellular plasticity during regeneration
• Therapeutic potential in regenerative medicine:
  • Modulating EMT to promote tissue repair
  • Preventing fibrosis by controlling EMT duration and intensity