EMT2

Question 1

Name the situations and the pathways that can then idnuce the master regulators of EMT

Answer 1

Physical Constrains, Hypoxia, Inflammation, Metabolic and Oncogenic Stress

NF-kB, TGF-B, HIF, Wnt, Ras, Notch

Question 2

What role does EMT have in early dissemination

Answer 2

Shown that pre-malignant crypt cells in CRC have been able to disseminatie –> EMT must undergo a role in this!

Question 3

What role does EMT have with the stromal niche

Answer 3

EMT promotes interaction with the stromal niche
Cell begins to undergo EMT –> moves into the stroma –> uses stomal signals to promote its own EMT –> secretes signals e.g. TGF-B to encourage other cells to also undergo EMT

Question 4

What are the 2 types of CSC

Answer 4

1) Proliferating

2) Dormatn

Question 5

Briefly describe normla kidney development

Answer 5

Wolfian duct gives rise to the ureteric bud
Metanephric mesenchyme surrounds the ureteric nud
TFs e.g. WT1 cause the mesenchyme to form kidney structure

Question 6

What happens in WIlms

Answer 6

Metanephric mesenchyme fails to undergo MET

Question 7

What genes are mutated in WIlms giving an unfavourable histology

Answer 7

SIX1/2
Drosha DGCR8
TP53

Question 8

Role of EMT in tissue repair/fbrosis

Answer 8

Doesnt occur in heart

But liver cells can undergo EMT and MET and form fibrotic tissue

Question 9

What is vimentin

Answer 9

An intermediate filament component of the mesenchyme cytoskelton

Question 10

What is fibronectin

Answer 10

An ECM protein

Question 11

What is N-Cadherin

Answer 11

Takes the place of E-Cadherin

Question 12

How does N-Cadherin promote tumour invasion

Answer 12

N-Cadherin has a strong affinity to other N-Cadherin Molecules. I.e. seen in melanoma where N-Cadherin whre n-Cadherin can help facilitate invasion of the dermal stroma

Question 13

How are the genetics of early development related to EMT

Answer 13

The genetics of early development help explain the genome changes required in EMT, most genes control key steps in embryogenesis
Snail, SLug and Twist were first identified in Drosophilia

Question 14

What additional function do slug and twist convey to cells

Answer 14

Both slug and twist are able to help cells resist apoptosis and anoikis in metastating cells –> this may suggests that invasiveness may simply be an exaggeration of the initial cell transformation.

Question 15

Desribe the different actions of WT1 on EMT and MET

Answer 15

Wt1 promotes MET through a KTS splice variant in the metanephric mesenchyme
Wt1 promotes EMT in the epicardial cells that generate the CV progenitor cells

Question 16

What are the actions of WT1 in ccRCC

Answer 16

ccRCC are often deficient of VHL ( A TSG)
WT1 –> upregulates Snail which then represses E-Cadherin
But WT1 can also promote E-Cadherin to mediate the effects of WT1
HEnce in this ccRCC WT1 has the effect of both promoting and inhibiting EMT.