Epithelial-Mesenchymal Transition Flashcards
How are epithelial cells linked to each other?
Tightly
Where is the junctional complex of epithelial cells located?
At the most apical part of the lateral membrane
What three components does the junctional complex of epithelial cells consist of?
Tight junctions, desmosomes and adherens junctions
List the components found in adherens junctions
F-actin Alpha- and beta-catenin E-cadherin p120ctn Vinculin Alpha-actinin VASP
Give an example of a transcriptional regulator involved in tight junctions
ZONAB
Give an example of a regulatory protein involved in tight junctions
G proteins
What is the main component found in tight junctions?
Actin filaments
Give an example of an adaptor protein involved in tight junctions
ZO-1
Give an example of a transmembrane protein involved in tight junctions
Occludin
What is the function of tight junctions?
To act as a barrier/fence
List the components found in desmosomes
Desmoplakin Desmoglein Desmocolin Plakophilin Plakoglobin
What makes up a desmosomal complex?
Desmoglein/desmocolin-plakoglobin-desmoplakin-filaments (intermediate)
What is EMT characterised by?
Loss of cell adhesion
Repression of E-cadherin expression
Increased cell motility
What are the changes that occur for epithelial cells to transition into mesenchymal cells?
Changes in gene regulation, cell adhesion and cytoskeletal organisation
Reduction in E-cadherin or increased vimentin
EMT is an irreversible process, true or false?
False, EMT is reversible
Where are EMT and MET often observed in normal human cells?
During embryonic development
At what stage in the linear tumour progression model is EMT observed?
In the change from a carcinoma to a metastatic tumour
Who came up with the theory of parallel progression of primary and secondary tumours?
Christoph Klein
What are the transcription factors that control EMT in embryonic development?
SNAIL SLUG ZEB1 ZEB2 TWIST1/2
What does SNAIL (SNAIL1) play a role in?
Gastrulation
What does SLUG (SNAIL2) play a role in?
Melanocytic lineage
Hematopoietic stem cells
What does ZEB2 (SIP1) play a role in?
Neural crest formation
What does ZEB1 (DeltaEF1) play a role in?
Bones and thymic T-cell development
What does TWIST1 play a role in?
Neural tube defects
How do the sizes of EMT transcription factors vary?
Between ~160 amino acids to ~1200 amino acids
List some domains commonly found in EMT transcription factors
CtBP binding site Zinc finger Homeodomain SNAG domain Serine-rich domain Nuclear export sequence Basic domain HLH domain Slug domain Twist box
What does ZEB2 induce in A431 cells and what is the affects of the zinc finger mutant?
Induces genetic reprogramming
Zinc finger mutant does not affect gene expression
What is a microRNA and what is it implicated in?
22 nt non-coding RNA species implicated in posttranscriptional regulation of gene expression
Binds to mRNA to stop translation or cause degradation of the mRNA
What microRNA family is ZEB1/2 expression regulated by?
miR-200
What microRNA is SNAIL expression regulated by?
miR-34
What do miR-200 and miR-34 link EMT with?
p53
Finish this sentence, p53 is a guardian of epithelial…
Identity
Give some properties of epithelial cells
Cell to cell adhesion
Low motility
E-cadherin/catenin
Do the same or different signalling pathways induce EMT transcription factors?
Different
Give some properties of mesenchymal cells
Cell-matrix interaction
High motility
N-cadherin/vimentin
MMPs/collagen
What does TGFbeta regulate?
The ZEB/miR-200 network
What are the phases of the cell cylce?
(G0), G1, S, G2, M
How does the DNA content change during S phase?
Increases progressively from 2N to 4N
What is the DNA content during G2 and M phase?
4N
How does mitosis affect the DNA content?
Allows the return to the normal 2N value for phases G0 or G1
What do the checkpoint controls check?
Am I OK to proliferate?
Is the previous phase completed?
Is this timely?
Is my DNA damaged?
Name a key protein involved in cell-cycle progression
Retinoblastoma protein
What transcription factor arrests cells in G1 phase?
ZEB2
How does ZEB2 arrest cells in G1?
By transcriptional repression of cyclin D1
Describe the correlation between cyclin D1 and ZEB2?
Inverse
What does SNAIL do in MDCK cells?
Downregulates D cyclins
Induces G1 cell cycle arrest
Give an example of an E-cadherin dominant negative mutant
EcWVM
G1-S transition is not affected in EMT induced by a dominant negative E-cadherin, true or false?
True
How do conventional cancer therapies work?
They induce DNA damage (via ATM or ATR)
What does ZEB2 delay in RT112 cells?
UV- and cisplatin-induced apoptosis
Response to radiotherapy in bladder cancer patients depends on the status of what transcription factor?
ZEB2
What are EMT-inducing transcription factors otherwise known as?
Oncogenes
What does TWIST1 facilitate the escape from?
Oncogene-induced senescence and apoptosis
What do EMT-inducing transcription factors block?
Oncogene-induced senescence
What cells do EMT programs generate which is in accordance with the definition of ‘cancer stem cells’?
More tumourigenic (escape anti-oncogenic barrier of premature senescence)
Slowly proliferating
Drug resistant
Master regulators of EMT control diverse cancer-related pathways, true or false?
True
