EMT/MET Flashcards
Why is EMT/MET a good area to study?
- required for embryonal development
- can be altered or reactivated in cancer
- could be a route of treatment
What are the 4 primary tissues?
- muscle
- connective tissue
- nerve tissue
- epithelial tissue
What are the characteristics of epithelial cells? (3)
- usually a single organised layer
- connected by tight adhesions that prevent migration from the monolayer
- regularly spaced junctions and adheions between cells
What are the 4 types of junction between epithelial cells?
- tight adhesions control passage of fluids and solutes and maintain cellular polarity by erstricting the movement of membrane proteins and lipids
- gap junctions direct cell-cell communication
- adherens junctions - contacts between cells
- desmosomes - mechanical strength ant stability in tissues under high mechanical pressure such as the skin and heart
- all allow the movement of nutrients ions and signalling molcules and maintain structure and adhesion
Why is epithelium important / what does it do? (4)
- maintains shape and structure
- absorption and secretion
- apical-basal polarity i.e the sides can interact with different molecules and perform different functions
- first protective layer against pathogens and damage
What are the characteristics of a mesenchymal cell? (5)
- lack of regimented structure
- stretched and elongated in shape
- often form irregular compositions and densities
- fewer tight junctions allow movement from the tissue
- can migrate and invade the basement membrane
What is EMT?
- epithelial to mesenchymal transition
- cell-cell and cell-ECM adhesions are lost to allow the cell to come away from the epithelial monolayer
- cytoskeleton rearrangements allow 3D movement of cells in teh ECM
- altered genetic program to maintain the new mesenchymal phenotype
- reversible process
Name 2 changes in cell structure seen in EMT
- from cortical actin to actin stress fibres
- polarity from apical-basal to front-back
What are the 3 types of EMT?
- development - cycles of EMT and MET involved in producing tissues during development
- chronic injury - cells undergo EMT to replace damaged cells due to injury - can become chronic
- malignancy - change in phenotype of tumour cells from epithelial to mesenchymal can allow them to migrate and metastasise
Describe one of the first EMTs in development
- production of the germ layers
- ectoderm - mesoderm EMT
- mesoderm - endoderm MET
- neural crest cells undergo MET to migrate around the body and form neurons
Give some examples of cells derived from mesoderm EMT and neural crest EMT
- mesoderm produces bone, muscles and blood
- neural crest produces neurons, glial cells and skeletal muscle
What signalling occurs in embryonic EMT gastrulation signalling?
- leads to mesoderm ingression
- TGF-B and nodal -> SMAD, slug snail and twist (downregulate e-cadherin and upregulate n-cadherin and other mesenchymal markers)
- Wnt -> B-catenin can also modulate these genes
- FGF activates MAPK/ERK and movement
What signalling occurs in embyronic EMT neural crest development?
- Wnt, notch and FGF
- notch involved in determining cell fate
- trigger enzymes and TFs such as sox9
- signalling cascade leading to neural crest delamination
How does Wnt act in EMT? as an example
- wnt can cause B-catenin to enter the nucleus and begin the transcription of SNAIL1/2 or activate other genes in EMT
How do inflammation and hypoxia lead to emt?
inflammation can signal STAT3 and cause EMT
hypoxia can signal Hif1-alpha and cause EMT
How can miRNAs regulate EMT-MET?
-transcriptional regulators act in feedback loops with miRNAs
- let-7 is essential for development and inhibits RAS and other oncogenes in MET
- epigenetic regulators such as polycomb proteins also interact with miR-200 and E-cadehin in feedback loops.
