Epithelial-Mesenchymal Transition

Question 1

How are epithelial cells linked to each other?

Answer 1

Tightly

Question 2

Where is the junctional complex of epithelial cells located?

Answer 2

At the most apical part of the lateral membrane

Question 3

What three components does the junctional complex of epithelial cells consist of?

Answer 3

Tight junctions, desmosomes and adherens junctions

Question 4

List the components found in adherens junctions

Answer 4

F-actin
Alpha- and beta-catenin
E-cadherin
p120ctn
Vinculin
Alpha-actinin
VASP

Question 5

Give an example of a transcriptional regulator involved in tight junctions

Answer 5

ZONAB

Question 6

Give an example of a regulatory protein involved in tight junctions

Answer 6

G proteins

Question 7

What is the main component found in tight junctions?

Answer 7

Actin filaments

Question 8

Give an example of an adaptor protein involved in tight junctions

Answer 8

ZO-1

Question 9

Give an example of a transmembrane protein involved in tight junctions

Answer 9

Occludin

Question 10

What is the function of tight junctions?

Answer 10

To act as a barrier/fence

Question 11

List the components found in desmosomes

Answer 11

Desmoplakin
Desmoglein
Desmocolin
Plakophilin
Plakoglobin

Question 12

What makes up a desmosomal complex?

Answer 12

Desmoglein/desmocolin-plakoglobin-desmoplakin-filaments (intermediate)

Question 13

What is EMT characterised by?

Answer 13

Loss of cell adhesion
Repression of E-cadherin expression
Increased cell motility

Question 14

What are the changes that occur for epithelial cells to transition into mesenchymal cells?

Answer 14

Changes in gene regulation, cell adhesion and cytoskeletal organisation
Reduction in E-cadherin or increased vimentin

Question 15

EMT is an irreversible process, true or false?

Answer 15

False, EMT is reversible

Question 16

Where are EMT and MET often observed in normal human cells?

Answer 16

During embryonic development

Question 17

At what stage in the linear tumour progression model is EMT observed?

Answer 17

In the change from a carcinoma to a metastatic tumour

Question 18

Who came up with the theory of parallel progression of primary and secondary tumours?

Answer 18

Christoph Klein

Question 19

What are the transcription factors that control EMT in embryonic development?

Answer 19

SNAIL
SLUG
ZEB1
ZEB2
TWIST1/2

Question 20

What does SNAIL (SNAIL1) play a role in?

Answer 20

Gastrulation

Question 21

What does SLUG (SNAIL2) play a role in?

Answer 21

Melanocytic lineage

Hematopoietic stem cells

Question 22

What does ZEB2 (SIP1) play a role in?

Answer 22

Neural crest formation

Question 23

What does ZEB1 (DeltaEF1) play a role in?

Answer 23

Bones and thymic T-cell development

Question 24

What does TWIST1 play a role in?

Answer 24

Neural tube defects

Question 25

How do the sizes of EMT transcription factors vary?

Answer 25

Between ~160 amino acids to ~1200 amino acids

Question 26

List some domains commonly found in EMT transcription factors

Answer 26

``` CtBP binding site Zinc finger Homeodomain SNAG domain Serine-rich domain Nuclear export sequence Basic domain HLH domain Slug domain Twist box ```

Question 27

What does ZEB2 induce in A431 cells and what is the affects of the zinc finger mutant?

Answer 27

Induces genetic reprogramming | Zinc finger mutant does not affect gene expression

Question 28

What is a microRNA and what is it implicated in?

Answer 28

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

Question 29

What microRNA family is ZEB1/2 expression regulated by?

Answer 29

miR-200

Question 30

What microRNA is SNAIL expression regulated by?

Answer 30

miR-34

Question 31

What do miR-200 and miR-34 link EMT with?

Answer 31

p53

Question 32

Finish this sentence, p53 is a guardian of epithelial...

Answer 32

Identity

Question 33

Give some properties of epithelial cells

Answer 33

Cell to cell adhesion Low motility E-cadherin/catenin

Question 34

Do the same or different signalling pathways induce EMT transcription factors?

Answer 34

Different

Question 35

Give some properties of mesenchymal cells

Answer 35

Cell-matrix interaction High motility N-cadherin/vimentin MMPs/collagen

Question 36

What does TGFbeta regulate?

Answer 36

The ZEB/miR-200 network

Question 37

What are the phases of the cell cylce?

Answer 37

(G0), G1, S, G2, M

Question 38

How does the DNA content change during S phase?

Answer 38

Increases progressively from 2N to 4N

Question 39

What is the DNA content during G2 and M phase?

Answer 39

4N

Question 40

How does mitosis affect the DNA content?

Answer 40

Allows the return to the normal 2N value for phases G0 or G1

Question 41

What do the checkpoint controls check?

Answer 41

Am I OK to proliferate? Is the previous phase completed? Is this timely? Is my DNA damaged?

Question 42

Name a key protein involved in cell-cycle progression

Answer 42

Retinoblastoma protein

Question 43

What transcription factor arrests cells in G1 phase?

Answer 43

ZEB2

Question 44

How does ZEB2 arrest cells in G1?

Answer 44

By transcriptional repression of cyclin D1

Question 45

Describe the correlation between cyclin D1 and ZEB2?

Answer 45

Inverse

Question 46

What does SNAIL do in MDCK cells?

Answer 46

Downregulates D cyclins | Induces G1 cell cycle arrest

Question 47

Give an example of an E-cadherin dominant negative mutant

Answer 47

EcWVM

Question 48

G1-S transition is not affected in EMT induced by a dominant negative E-cadherin, true or false?

Answer 48

True

Question 49

How do conventional cancer therapies work?

Answer 49

They induce DNA damage (via ATM or ATR)

Question 50

What does ZEB2 delay in RT112 cells?

Answer 50

UV- and cisplatin-induced apoptosis

Question 51

Response to radiotherapy in bladder cancer patients depends on the status of what transcription factor?

Answer 51

ZEB2

Question 52

What are EMT-inducing transcription factors otherwise known as?

Answer 52

Oncogenes

Question 53

What does TWIST1 facilitate the escape from?

Answer 53

Oncogene-induced senescence and apoptosis

Question 54

What do EMT-inducing transcription factors block?

Answer 54

Oncogene-induced senescence

Question 55

What cells do EMT programs generate which is in accordance with the definition of 'cancer stem cells'?

Answer 55

More tumourigenic (escape anti-oncogenic barrier of premature senescence) Slowly proliferating Drug resistant

Question 56

Master regulators of EMT control diverse cancer-related pathways, true or false?

Answer 56

True