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Cancer > Invasion – Regulation of Cell Motility > Flashcards

Invasion – Regulation of Cell Motility Flashcards

1
Q

What are the changes that occur in the cells that occur during tumour progression?

A
  1. Homeostasis
  2. Genetic alterations
  3. Hyperproliferation
  4. De-differentiation
    - disassembly of cell-cell contacts
    - loss of polarity
  5. Invasion
    - increased motility
    - cleavage of ECM proteins
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2
Q

What are the different types of tumour cell migration, giving examples?

A

Individual cell migration:

  1. Ameboid e.g lymphoma
  2. Mesenchymal (single) e.g fibrosarcoma

Collective cell migration:

  1. Mesenchymal (chains) e.g fibrosarcoma
  2. Clusters/cohorts e.g epithelia cancers
  3. Multicellular strands/sheets e.g epithelial cancers
    - collective cell migration requires more coordination to metastasise and so still has some cell-cell junctions
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3
Q

What physiological phenomena does tumour migration mimic?

A

Morphogenesis e.g. angiogenesis

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4
Q

What did a comparison of the expression profile of invasive cells vs primary tumours show to be upregulated in invasive cells with the administration of epidermal growth factor (EGF)?

A

Cytoskeleton regulation

Motility machinery

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5
Q

What makes normal migrating cells stop moving?

A

Contact inhibition of locomotion

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6
Q

How are tumour cells different in this aspect?

A

They lose contact inhibition of locomotion so they can multilayer

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7
Q

What is another term for ECM proteins?

A

Substratum

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8
Q

What are filopodia?

A
  • fingerlike projections found on the leading edge of migrating cells.
  • form focal adhesions to the substratum and are pulled forward by treadmilling of actin fibres.
  • also sense local environment
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9
Q

What are lamellipodia?

A

Sheet-like protrusions that are rich in actin filaments

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10
Q

What are the four main stages of cell movement?

A

Extension
Adhesion
Translocation
De-adhesion

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11
Q

What are the attachments between the cell and the surface that it is moving along called?

A

Focal adhesions

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12
Q

What are the monomers of actin filaments?

A

G-actin

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13
Q

Describe the polarity of acting filaments.

A

They have a plus end and a minus end

The monomers preferentially get added on at the plus end

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14
Q

What protein complex is important in initiating polymerisation?

A

Arp2/3

This forms a trimer with actin and is good at initiating polymerisation

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15
Q

What is the limiting step in actin dynamics?

A

Nucleation
Attachment of the actin to the cell inner membrane
Formation of ARP2/3-actin trimers to initiate polymerisation (ARPs bind to minus end)

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16
Q

State two proteins that bind to free G-actin and describe how they affect elongation.

A

Elongation
Profilin facilitates actin monomer binding to the actin filament
Thymosin reduces actin monomer binding by sequestering the free monomers so they are not available to bind the to actin filament

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17
Q

What is capping? Name some + end capping proteins.

A
  • addition of a capping molecule (to + or - end) to limit elongation
    CapZ
    Gelsolin
    Fragmin/severin
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18
Q

Name some – end capping proteins.

A

Tropomodulin

Arp2/3

19
Q

What is severing? Name some severing proteins.

A
  • breaking up actin filaments
    Gelsolin ADF
    Framin/severin
    Cofilin
20
Q

What are the features of the actin filaments in severed populations?

A

Actin filaments can grow and shrink more rapidly

21
Q

What can happen to single filaments of actin to improve their structural integrity?

A

They can be bundled or cross-linked

22
Q

Name some proteins involved in the cross- linking and bundling of actin process.

A 
Alpha-actinin 
Fimbrin 
Filamin 
Spectrin 
Villin 
Vinculin
23
Q

Which protein allows branching of the actin filaments?

A

Arp complex (Arp2/3)

24
Q

At what angle do they branch?

A

70 degrees

25
Q

Summarise the actions of Arp2/3.

A

They initiate nucleation
They cap filaments
They cause branching

26
Q

Describe what causes the gel-sol transition.

A

The actin filaments can be severed to make the cell more fluid

  • gels are rigid and have NOT been severed
  • sols are not rigid (can flow) and HAVE been severed
27
Q

Describe the actin processes that take place during the protusion of lamellipodia.

A

There is polymerisation, disassembly, branching and capping
There is net filament assembly at the leading edge

28
Q

Describe the actin processes that take place during the formation of filopodia.

A

Actin polymerisation
Bundling and cross-linking
(NO branching)
As soon as the finger wants to retract it will collapse at the base

29
Q

State four signalling mechanisms that regulate the actin cytoskeleton.

A
  1. Ion flux changes
  2. Phosphoinositide signalling
  3. Kinases/phosphatases
  4. Small GTPases
30
Q

What are the three most important small GTPases in terms of the actin cytoskeleton and what does activation of each cause?

A

Cdc42 – filopodia production
Rac – lamellipodia production
Rho – stress fibre production
NOTE: these are all part of the Ras super family

31
Q

Explain how Rac causes actin polymerisation/organisation.

A

Rac binds to and activates WAVE

WAVE then activates Arp2/3, which is important in actin organisation

32
Q

Explain how Cdc42 causes actin polymerisation/organisation.

A

Cdc42 binds to WASP

WASP also activates Arp2/3

33
Q

Which small GTPases are involved in lamellipodia protrusion?

A

Rac

34
Q

Which small GTPases are involved in focal adhesion assembly?

A

Rac and Rho

35
Q

Which small GTPases are involved in contraction?

A

Rho (stress fibres are important for contraction)

36
Q

What do cells use for motility?

A

Filopodia
Lamellipodia
Focal adhesions

37
Q

What is control in motility needed for?

A
  1. coordinate what is happening in different parts in the cell
  2. regulate adhesion/release of cell-extracellular matrix receptors
  3. to respond to external influences –
    sensors
    directionality
38
Q

What protein do cells attach to the ECM via?

A

Integrins

39
Q

What are some stimuli to move a cell?

A
  1. organogenesis and morphogenesis
  2. wounding
  3. growth factors/chemoattractants
  4. dedifferentiation (tumours)
40
Q

How do cells know where to go?

A

Polarity

41
Q

What is the polymer form of actin

A

linear polymer microfilament called F-actin (filamentous)

42
Q

How are actin filaments polar?

A

The two ends of an actin filament differ in their dynamics of subunit addition and removal.

  • referred to as the plus end (with faster dynamics, also called barbed end
  • minus end (with slower dynamics, also called pointed end). …
  • as a consequence, the actin filaments are also structurally polar.
43
Q

Describe the structure of integrins?

A
  • heterodimer complexes that contain both α and β subunits.
  • recognise short, specific peptide sequences and associate extracellularly by their “head” regions.
  • “tail” regions span the entire plasma membrane.

Cancer (15 decks)

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