Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Cancer > Invasion - regulation of cell migration > Flashcards

Invasion - regulation of cell migration Flashcards

1
Q

State the steps of (epithelial) tumour progression

A
  1. Homeostasis
  2. Genetic alterations
  3. Hyper-proliferation
  4. De-differentiation (disassembly of cell-cell contacts and loss of polarity)
  5. Invasion (increased motility and cleavage of ECM proteins)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the 5 different types of tumour cell migration? State important cell membrane proteins/structures required for collective and individual cell migration

A
  1. Single cell migration (as an ameboid)
  2. Mesenchymal single cells
  3. Mesenchymal chains
  4. Clusters/cohorts
  5. Multicellular strands/sheets
  • Integrins and proteases for both collective and individual migration
  • Cadherins and gap junctions for just collective migration
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What physiological phenomena does tumour migration mimic?

A

Morphogenesis e.g. angiogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What did a comparison of the expression profile of invasive cells vs primary tumours show to be upregulated in invasive cells?

A

Upregulation of genes involved in:

  • Cytoskeleton regulation
  • Motility machinery
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What give normal migrating cells directionality and what makes normal migrating cells stop moving?

How are tumour cells different in this aspect?

A

Polarity determines what direction they move in. Contact inhibition of locomotion = STOP.

They lose contact inhibition of locomotion so they can multilayer.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are main stimuli for cells to migrate?

A
  • organogenesis + morphogenesis
  • wounding
  • growth factors/chemoattractants
  • dedifferentiation (tumours)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Define substratum

A

A surface (ECM proteins) in which the cell attaches to, especially when the cell is growing or moving

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Attachment of cells to substratum

allows them to move - how?

A
  • Focal adhesions hook onto ECM + provide holding for cell whilst move
  • Hooking mostly done by integrins
  • Focal adhesions are on terminal ends of actin filament
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are filopodia?

A

Finger-like protrusions that are rich in actin filaments

They sense the local environment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are lamellipodia?

A

Sheet-like protrusions that are rich in actin filaments

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Define haptotaxis

A

Haptotaxis is a directional cell movement in response to adhesive substrates such as ECM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the processes of cell motility?

A
  • Extension of cell in direction of movement
  • Adhesion: led by lamellipodium, then filopodia hook onto ECM to form new focal adhesion
  • Translocation: active contraction of cell to bring the rear of the cell forwards
  • De-adhesion of previous focal adhesion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the small subunits/monomers that make up the actin filament polymers/F-actin?

A

G-actin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe how Actin filament polarity affects the cell movement.

A

In response to signal (e.g. nutrients) F actin disassembles and then reassembles on the side of the cell near the signal => cell polarity => allows movement

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe the organisation and structure of the filament in the filopodia and lamellipodia? What are stress fibres?

A
  • Filopodia filled with bundles of parallel actin filaments
  • Lamellipodia have branched and cross-linked filaments
  • Stress fibres have antiparallel filament organisation; they are contractile structures and have focal adhesions on endings
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What protein complex is important in initiating polymerisation? What is the name of the process?
How do the monomers get added on?

A

ARP complex (composed of Arp2, Arp3 and other proteins)

Arp 2 and 3 form a trimer with actin to initiate polymerisation - called nucleation.

They have a plus end and a minus end; monomers preferentially get added on at the plus end

17
Q

Hence, what is the limiting step in actin dynamics?

A

Formation of Arp2/3-actin trimers to initiate polymerisation

18
Q

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

A

Profilin - these deliver the G-actin to the growing filament => promote elongation

Beta4 thymosin and ADF/cofilin - they sequester G-actin but do not inhibit polymerisation

19
Q

Name some capping proteins that bind at the plus end.

A

CapZ
Gelsolin
Fragmin/severin

20
Q

Name some capping proteins that bind at the minus end

A

Tropomodulin

Arp2/3

21
Q

Name some F-actin severing proteins.

A

Gelsolin
Fragmin/severin
ADF/Cofilin

22
Q

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

A

Actin filaments can grow and shrink more rapidly

23
Q

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

A

They can be bundled or cross-linked

24
Q

Name some proteins involved in actin filament bundling and cross-linking. How are they involved?

A
  • Alpha-actinin (dimers cross link filaments)
  • Fimbrin
  • Filamin (filaments are at angles from each other => mesh)
  • Spectrin (filaments are at angles from each other => mesh)
  • Villin
  • Vinculin
  • Dystrophin (links filaments to plasma membrane)
25
Q

Which protein allows branching of the actin filaments?

A

Arp complex (binds somewhere along the filament and initiates new polymerisation at an angle)

26
Q

At what angle do the filaments branch (due to Arp)?

A

70 degrees

27
Q

Summarise the actions of the Arp complex.

A

They bring about nucleation
They cap filaments (minus end)
They cause branching

28
Q

Describe what causes the gel-sol transition.

A

The actin filaments can be severed to make the cell more fluid
Gel (rigid) => Sol (can flow)

29
Q

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

A

There is disassembly, nucleation, branching, severing, capping and bundling
There is net filament assembly at the leading edge and net filament disassembly behind the leading edge

30
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

31
Q

State four signalling mechanisms that regulate the actin cytoskeleton.

A
  1. Ion flux changes (i.e. intracellular calcium)
  2. Phosphoinositide signalling (phospholipid binding)
  3. Kinases/phosphatases (phosphorylation cytoskeletal proteins)
  4. Signalling cascades via small GTPases
32
Q

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

A

Cdc42 – for filopodia
Rac – for lamellipodia protrusion
Rho – for stress fibres

NOTE: these are all part of the Rho sub-family which belongs to the Ras super-family

33
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

34
Q

Explain how Cdc42 causes actin polymerisation/organisation.

A

Cdc42 binds to WASP

WASP also activates Arp2/3

35
Q

Which small GTPases are involved in focal adhesion assembly?

A

Rac and Rho

36
Q

Which of the small GTPases are involved in contraction required for cell movement?

A

Rho (as stress fibres are important for contraction)

Cancer (15 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions