Metastasis Flashcards

1
Q

Tumours often arises in what kind of tissue?

A

epithelial

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2
Q

What tissue layer is beneath epithelial layer?

A

Connective tissue

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3
Q

What is the connective tissue made of?

A

Fibroblasts, secreted growth factors

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4
Q

What is beneath the connective tissue layer?

A

Another epithelial layer followed by Capillaries

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5
Q

The basement membrane is the layer that epithelial cells sits on is made of what?

A

ECM

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6
Q

Cells form interactions with extracellular proteins via what?

A

Integrins (claps)

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7
Q

Cell-cell interactions are made via what?

A

Cadherins

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8
Q

What happens to cyclin A expression when integrin signalling is disrupted?

A

Cyclin A can be produced without anchorage

The affect on p27 is the reverse

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9
Q

Describe integrin?

A

Heterodimeric TM protein with large extracellular domain and small intracellular domain

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10
Q

How many alpha and beta subunits exist for integrin?

A

15 alpha
8 beta
can exist in many conformations - affect what it can interact with in the ECM

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11
Q

Give examples of proteins that integrins interact with?

A

actin and signalling molecules (e.g. ILK, FAK)

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12
Q

What pathways can ILK (integrin linked kinase) mediate?

A

cyclin D expression, AKT pathway, cadherin signalling and actin cytoskeleton

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13
Q

What ion is cadherin sensitive to?

A

Ca2+, gives cadherin rigidity

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14
Q

Do cadherins respond to extracellular or intracellular Ca2+?

A

Extracellular

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15
Q

What does cadherin rigidity allow?

A

Interaction cadherins on neighbouring cells

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16
Q

Cadherin interactions are anti-proliferative. True or False?

A

True

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17
Q

What is the most common cadherin?

A

E-cadherin

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18
Q

Is cadherin a tumour suppressor or oncogene?

A

Tumour suppressor

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19
Q

What binds the intracellular part of cadherin?

A

beta catenin
alpha catenin
p120 catenin

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20
Q

Which GTPases are p120 able to bind to?

A

RhoA
Rac
cdc42

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21
Q

What is the function of RhoA?

A

form stress fibres - associated with increased motility

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22
Q

What is the function of Rac?

A

Causes formation of lamellipodia

23
Q

What is the function of cdc42?

A

Causes formation of filopodia

24
Q

What do lamellipodia and filopodia cause generally?

A

check local environment and retract when they encounter cells

25
Q

Describe structure of beta-catenin.

A

Many alpha helical turns (armadillo repeats)

26
Q

Where can beta catenin be found in the cell?

A

Membrane bound or cytoplasmic

27
Q

What happens to cytoplasmic beta catenin?

A

Gets degraded via APC and GSK3

28
Q

What is familial adenomatous polyposis?

A

APC mutations (present in 80% of colon cancers) and gives rise to polyps and can form cancer

29
Q

Where is the beta catenin binding site in APC?

A

N terminal - cancerous mutations occur here

30
Q

Why does beta catenin have a NLS?

A

When beta catenin is not bound to cadherin in healthy cells it indicates a lack of cell-cell interaction and hence that proliferation is required to build monolayer

31
Q

What does beta catenin interact with the nucleus?

A

TCF/LEF

32
Q

What is TCF/LEF?

A

TF with no DNA binding site (only transactivation domain)

33
Q

What does TCF/LEF/beta-catenin express?

A

D cyclins, c-MYC, MMPs

34
Q

what is the affect of wnt signalling on beta catenin?

A

stabilises beta catenin

35
Q

Intracellular cadherin truncations result in what?

A

Higher concentrations of Cytoplasmic beta

36
Q

What is the affect of ILK on GSK3?

A

ILK inhibits GSK3 - how integrin and cadherin signalling links

37
Q

What is EMT?

A

epithelial mesenchymal transition - cells losing E-cadherin - occurs in development and cancer progression

38
Q

What are metallomatrix proteins?

A

MMP are required for movement through ECM - proteases that cleave substrates at hydrophobic residues

39
Q

What activates MMP expression?

A

beta catenin/TCF/LEF

40
Q

Where are MMP produced?

A

RER then shuttled to surface

41
Q

Some MMPs are TM with cytoplasmic tails. True or False?

A

True - however most are secreted

42
Q

MMPs have the different accessory domains but the same what?

A

catalytic fold

43
Q

Name an accessory domains in MMP?

A

Haemopexin - recruits substrate

44
Q

What is the catalytic domain motif that coordinates a zinc ion?

A

HEXGHXXGXXH

45
Q

What is the prodomain of an MMP?

A

PRCGXPD motif - cysteine binds to a zinc ion and blocks catalytic site inactivating it

46
Q

Different MMPs have different substrates but all cleave what type of protein?

A

ECM proteins

e.g. collagen, gelatine, elastin

47
Q

What residues do MMP cleave at?

A

V M F I L - these are common and so proteins get cleaved into small peptides that don’t hinder cell movement

48
Q

Are MMP’s potential drug targets?

A

Yes - if hinder cell mobility is reduced hence restricting metastasis

49
Q

What is the seed soil theory?

A

Primary tumour locations are associated with specific secondary locations

50
Q

Give an example of a seed and soil.

A

Lung –> brain

51
Q

What does secretion of IL-11 do?

A

causes osteoclast activation to make room for tumour colonisation in bones

52
Q

Secreting lysyl oxidase has what affect on osteoclast?

A

Causes lysine in collagen to form aldehydes which favours osteoclast

53
Q

Why are exosomes relevant to cancer?

A

Vesicles used by cancer to prepare sites of metastasis. Exosomes target integrins and deliver cargo that favour metastatic colonisation