EMT

Question 1

EMT definition

Answer 1

loss of epithelial cell polarity, junctions and adhesions to gain migratory and invasive properties and form mesenchymal cells

common in the formation and metastasis of carcinomas

Question 2

3 types of EMT

Answer 2

1. MESENCHYMAL:
   - neural tube in the third week of gestation release cells forming neural crest that have epithelial origin but then migrate via EMT and become mesenchymal and responsible of CT
   -gastrulation: formation of the mesoderm occurs via EMT of the uper germ layer cells
2. FIBROBLAST: wound healing, slightly more pathological: epithelial cells become fibroblasts accummulating collagen for fibrosis
3. METASTATIC: carcinoma development and metastasis - destruction of basement membrane and movement intoblood vessels of underlying CT to migrate

Question 3

characteristic epithelial markers

Answer 3

e-cadherins
cytokeratins
occludins and ZO1
desmoplakins
lamin

Question 4

characteristics mesenchymal markers

Answer 4

n-cadherins
vimentin
fibronectin
alpa SMA
collagen type 1
MMPs

Question 5

change in actin cytoskeleton over the EMT process

Answer 5

cortical actin in epithelial cells is lost and reverted into bundles of actin filaments in fibroblasts that optimise motility

Question 6

what triggers the EMT process

Answer 6

upregulation of certain transcription factors like snail and twist

Question 7

what is the result of MMP upregualation in the mesenchymal cells produced

Answer 7

matrix metalloproteinases
destroy components of ECM
allows increased cell motility

Question 8

2 types of carcinomas examples

Answer 8

1. renal cell: loss of e-cadherin and B-catenin, express vimentin but actin is still present –> no defined phenotype
2. pancreatic cell: very agressive, e-cadherin/B-catenins are still expressed, negative for vimentin BUT express proteins that destroy basemement membrane

!! this occurs because cells do not become completely mesenchymal or epithelial –> EMT is NOT a not-or-all process so there are intermediate phenotypes

Question 9

process of analysis of the carcinomas formed

Answer 9

2D monolayer or 3D spheroid models: analysis of the diff factors expressed and the degree of their expression