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CANKER - OBG > Regulation of Cell Motility > Flashcards

Regulation of Cell Motility Flashcards

1
Q

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

A

Genetic alterations lead to:

  • hyperproliferation,
  • disassembly of cell-cell contacts,
  • loss of polarity,
  • increased motility
  • cleavage of ECM proteins
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2
Q

What are the different types of tumour cell migration?

A

Single cell migration:

  • ameboid
  • Mesenchymal single cells

collective cell migration:

  • Mesenchymal chains
  • Clusters/cohorts
  • Multicellular strands/sheets
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3
Q

What physiological phenomena does tumour migration mimic?

A

Morphogenesis e.g. angiogenesis

repairing a scratch wound- primary glial cells

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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? (shown by administering 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

Finger-like protrusions that are rich in actin filaments

They sense the 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 (F-actin when polymerised)

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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/ nucleation ?

A

Arp2/3

This forms a trimer with actin and is good at initiating nucleation (ARP’s bing negative end of actin strand)

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15
Q

What is the limiting step in actin dynamics?

A

Formation of Arp2/3-actin trimers to initiate polymerisation/nucleation

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16
Q

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

A

Promote elongation – profilin (these deliver the G-actin to the growing filament)
Sequesters G-actin (inhibits elongation) –thymosin

17
Q

Name some + end capping proteins.

A

CapZ

Gelsolin

Fragmin/severin

18
Q

Name some – end capping proteins.

A

Tropomodulin

Arp2/3

19
Q

Name some severing proteins.

A

Gelsolin
Fragmin/severin
Cofilin/ADF

20
Q

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

A

Actin filaments can grow and shrink more rapidly

unsecured shrink/grow slowly

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 these processes.

cross linking and bundling

A 
Alpha-actinin 
Fimbrin 
Filamin 
Spectrin 
Villin 
Vinculin
23
Q

Which protein allows branching of the actin filaments?

A

Arp2/3 (Arp complex)

24
Q

At what angle do they branch?

A

70 degree

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
Gel=rigid
sol=more fluid/less rigid

27
Q

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

A

There is polymerisation/nucleation,
elongation,
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  
elongation
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

Ion flux changes
Phosphoinositide signalling ie phospholipid binding
Kinases/phosphatases
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
Rac – lamellipodia
Rho – stress fibres

NOTE: these are all part of the Rho family

31
Q

Which small GTPases are involved in lamellipodia protrusion?

A

Rac

32
Q

Which small GTPases are involved in focal adhesion assembly?

A

Rac and Rho

33
Q

Which small GTPases are involved in contraction?

A

Rho (stress fibres are important for contraction)

34
Q

what are the stimuli to move a cell

A

organogenesis
wounding
growth factor/ chemoattractants
de-differentiation

CANKER - OBG (14 decks)

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