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Flashcards in Invasion Deck (35):
1

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

Genetic alterations lead to hyperproliferation, disassembly of cell-cell contacts, loss of polarity, increased motility and cleavage of ECM proteins

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2. What are the different types of tumour cell migration?

Single cell migration (ameboid)
Mesenchymal single cells
Mesenchymal chains
Clusters/cohorts
Multicellular strands/sheets

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3. What physiological phenomena does tumour migration mimic?

Morphogenesis e.g. angiogenesis

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

Cytoskeleton regulation
Motility machinery

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5. What makes normal migrating cells stop moving?

Contact inhibition of locomotion

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6. How are tumour cells different in this aspect?

They lose contact inhibition of locomotion so they can multilayer

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7. What is another term for ECM proteins?

Substratum

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8. What are filopodia?

Finger-like protrusions that are rich in actin filaments
They sense the local environment

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9. What are lamellipodia?

Sheet-like protrusions that are rich in actin filaments

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10. What are the four main stages of cell movement?

Extension
Adhesion
Translocation
De-adhesion

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

Focal adhesions

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12. What are the monomers of actin filaments?

G-actin

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13. Describe the polarity of acting filaments.

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

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14. What protein complex is important in initiating polymerisation?

Arp2/3
This forms a trimer with actin and is good at initiating polymerisation

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15. What is the limiting step in actin dynamics?

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

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

Promote elongation – profilin (these deliver the G-actin to the growing filament)
Sequesters G-actin – Beta4 thymosin ADF, cofilin

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17. Name some + end capping proteins.

CapZ
Gelsolin
Fragmin/severin

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18. Name some – end capping proteins.

Tropomodulin
Arp2/3

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19. Name some severing proteins.

Gelsolin ADF
Framin/severin
Cofilin

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

Actin filaments can grow and shrink more rapidly

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

They can be bundled or cross-linked

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22. Name some proteins involved in these processes (bundling and cross linking)

Alpha-actinin
Fimbrin
Filamin
Spectrin
Villin
Vinculin

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23. Which protein allows branching of the actin filaments?

Arp2/3

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24. At what angle do they branch?

70 degrees

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25. Summarise the actions of Arp2/3.

They initiate nucleation
They cap filaments
They cause branching

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26. Describe what causes the gel-sol transition

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

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

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

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

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

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29. State four signalling mechanisms that regulate the actin cytoskeleton.

Ion flux changes
Phosphoinositide signalling
Kinases/phosphatases
Small GTPases

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

Cdc42 – filopodia
Rac – lamellipodia
Rho – stress fibres
NOTE: these are all part of the Rho family

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31. Explain how Rac causes actin polymerisation/organisation.

Rac binds to and activates WAVE
WAVE then activates Arp2/3, which is important in actin organisation

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32. Explain how Cdc42 causes actin polymerisation/organisation.

Cdc42 binds to WASP
WASP also activates Arp2/3

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33. Which small GTPases are involved in lamellipodia protrusion?

Rac

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34. Which small GTPases are involved in focal adhesion assembly?

Rac and Rho

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35. Which small GTPases are involved in contraction?

Rho (stress fibres are important for contraction)