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Cancer LCRS > Factors Controlling Cell Behaviour > Flashcards

Factors Controlling Cell Behaviour Flashcards

1
Q

What are the two types of external influences?

A

Chemical and physical

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2
Q

What are the chemical external influences on cells?

A 
Hormones
GF
Ion conc
ECM
Nutrients
Dissolved gas conc
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3
Q

What are the physical external influences on cells?

A

Mechanical stress
Temperature
Layout of ECM + other cells (topography)

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4
Q

What is anchorage dependence?

A 
The need for cells to adhere to a large area of ECM in order to:
Respond to GF
Proliferate
Produce protein
Determine phenotype 
Survive
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5
Q

How do cells bind to the ECM? Describe this receptor

A

Via integrins - transmembrane alpha beta heterodimer
Head (alpha and beta) binds to ECM ligands
Short tail binds to actin

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6
Q

How do integrins know where to bind onto ECM?

A

They recognise short peptide sequences

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7
Q

Name a common peptide sequence found on more than one ECM

A

RGD sequence (arg-gly-asp)

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8
Q

Which integrin binds to RGD?

A

Alpha 5 beta 1 fibronectin receptor binds to arg-gly-asp

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9
Q

What do a cluster of integrin complexes form?

A

Focal adhesions or hemidesmosomes

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10
Q

Give an example of an integrin found in epithelial hemidesmosomes

A

Alpha 6 beta 4

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11
Q

How many combinations of alpha beta integrin chains are known?

A

20 combinations

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12
Q

Name an integrin which binds to endothelial cells

A

Alpha 2b beta 2 can bind to ICAM-1 on endothelial cells

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13
Q

Name an integrin which binds to CD31

A

Alpha v beta 3 binds to PECAM - 1 (CD31)

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14
Q

What do hemidesmosomes bind to?

A

Intermediate cytoskeletal filament (not main actin)

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15
Q

What is outside in signalling?

A

Info about the surrounding ECM will determine the integrin complexes which bind, and thus the phenotype of the cell

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16
Q

What can open up integrins so that other molecules can bind?

A

Mechanical stress

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17
Q

How do integrins signal downstream?

A

They don’t have intrinsic signalling capacity, but they can recruit proteins.

18
Q

Name two key signalling proteins recruited by integrins and what they do

A

Focal Adhesion kinase - phosphorylates Src

Src

19
Q

What is inside out signalling?

A

Signal from inside the cell can influence the confirmational shape of the integrin

20
Q

Describe the conformational change in integrins which increase their affinity for ECM

A

Legs bent = low affinity

Legs flexed = high affinity

21
Q

Which factors determine cell population?

A

Contact inhibition

Competition for growth factors (density dependence)

22
Q

What is density dependence?

A

Competition for growth factors at high densities can limit cell populations

23
Q

What is the significance of anchorage dependence and density dependence?

A

(Signals from ECM and soluble GF.)

They both converge to promote proliferation. Individually, the activation is weak, but together, the activation is stronger and sustained.

24
Q

Describe the two types of interactions between cells

A

Short term contact - no cell cell junctions

Long term - cell cell junctions

25
Q

What is contact inhibition of locomotion?

A

When cells touch each other, they inhibit motility at the contact side and promote motility at the other side, so that the cells don’t crawl over each other.

26
Q

Which normal cells usually do not have contact inhibition of locomotion and why?

A

Epithelial cells, as they usual form monolayers

27
Q

List the cell cell junctions formed between epithelial cells

A 
Zonula = continuous belts
Macula = discrete spots
Tight junctions
Adherens
Desmosomes
Gap junctions
28
Q

What is an important link between cell cell adhesion and proliferation?

A

Beta catenin

29
Q

What are the effects of cell cell adhesion?

A

Reduced proliferation via inactive MAPK and increased p27KIP1

30
Q

Describe how cytoplasmic beta catenin is associated with junctions

A

Calcium dependent homophilic cadherin hinds to beta catenin, which binds to alpha catenin, which binds to actin

31
Q

What degrades beta catenin?

A

APC

32
Q

What happens when APC is inactive?

A

There’s nothing to degrade beta catenin, so it binds to LEF-1 and promotes gene transcription

33
Q

How else can cadherins influence proliferation?

A

Cluster of cadherins can alter GTPase activation

34
Q

Give examples of GTPases altered by cadherins following cell cell contact

A

Rac can be activated (actin polymerisation)

Rho can be invited (involved in contraction of cells during movement)

35
Q

What is an important consequence of loss of contact inhibition?

A

Metastasis

36
Q

Describe the loss of social skills of cells that can lead them to become cancerous

A 
Loss of density dependence
Loss of contact inhibition of locomotion
Loss of anchorage dependence
Break down of cell cell contacts
No Hayflick limit
Expression of telomerase
37
Q

What can cancerous cells produce to cleave through basal lamina and ECM?

A

Matrix metalloproteinases (MMPs)

38
Q

What is the most common origin of cancerous cells?

A

Epithelial cells

39
Q

What is the main family of GTPases?

A

Rho family!

40
Q

What signals the formation of filopodia?

A

Cdc42

Stretch your legs and get that will you!

41
Q

What controls the formation of lamellipodia and focal adhesions?

A

Rac

42
Q

What is the main GTPase involved in stress fibres?

A

Rho

NO I’m stressed!

Cancer LCRS (10 decks)

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