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YR2: MCD Cancer > Invasion – Regulation of Cell Motility > Flashcards

Invasion – Regulation of Cell Motility Flashcards

1
Q

What changes 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? Give examples of types of cancer that behave in this way

A

Single cell migration (ameboid) e.g. Leukaemia
Mesenchymal single cells e.g. Fibrosarcoma
Mesenchymal chains e.g. Glioblastoma
Clusters/cohorts e.g. Melanoma
Multicellular strands/sheets e.g. Vascular tumours

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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?

A

Cytoskeleton regulation

Motility machinery

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5
Q

What makes normal migrating cells stop moving? How are tumour cells different in migrating?

A

Contact inhibition of locomotion

Tumour cells lose contact inhibition of locomotion so can multilayer

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6
Q

What is another term for ECM proteins?

A

Substratum

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7
Q

What are filopodia?

A

Finger-like protrusions rich in actin filaments

Sense the local environment

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8
Q

What are lamellipodia?

A

Sheet-like protrusions rich in actin filaments

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9
Q

What are the four main stages of cell movement?

A

Extension
Adhesion
Translocation
De-adhesion

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10
Q

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

A

Focal adhesions

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11
Q

What are the monomers and polymers of actin filaments?

A

Monomers: G-actin
Polymers: F-actin

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12
Q

Describe the polarity of actin filaments.

A

They have a plus end + a minus end

Monomers preferentially get added on at the plus end

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13
Q

What protein complex is important in initiating polymerisation?

A

Arp2/3

Forms a trimer with actin, cell thinks there is a trimer, this facilitate rapid nucleation + initiates polymerisation

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14
Q

What is the limiting step in actin dynamics?

A

Formation of Arp2/3-actin trimers to initiate polymerisation

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15
Q

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

A

Promote elongation: profilin (deliver G-actin to the growing filament)
Sequesters G-actin: Beta–4 thymosin, ADF, cofilin

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16
Q

Name 3 + end capping proteins.

A

CapZ
Gelsolin
Fragmin/ severin

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17
Q

Name 2 – end capping proteins.

A

Tropomodulin

Arp2/3

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18
Q

Name 3 severing proteins.

A

Gelsolin
Framin/ severin
ADF/ Cofilin

19
Q

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

A

Actin filaments can grow + shrink more rapidly (than unsevered populations)

20
Q

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

A

They can be bundled or cross-linked

21
Q

Name 6 proteins involved in cross linking and bundling actin.

A 
Alpha-actinin 
Fimbrin 
Filamin 
Spectrin 
Villin 
Vinculin
22
Q

Which protein allows branching of the actin filaments?

A

Arp2/3

23
Q

At what angle do actin filaments branch?

A

70 degrees

24
Q

Summarise the actions of Arp2/3.

A

Initiate nucleation
Cap filaments
Cause branching

25
Q

Describe what causes the gel-sol transition.

A

Actin filaments can be severed to make the cell more fluid

26
Q

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

A

Polymerisation, disassembly, branching + capping

Net filament assembly at the leading edge + net filament disassembly behind leading edge

27
Q

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

A

Actin polymerisation
Bundling + cross-linking
(NO branching)
Capping at the projecting end + disassembly at the bottom of the protrusion allows retraction back to the membrane

28
Q

State four signalling mechanisms that regulate the actin cytoskeleton.

A

Ion flux changes (intracellular calcium)
Phosphoinositide signalling (phospholipid binding)
Kinases/phosphatases (phosphorylation cytoskeletal proteins)
Signalling cascades via small GTPases

29
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
(all part of the Rho family)

30
Q

Explain how Rac causes actin polymerisation/organisation.

A

Rac binds to + activates WAVE

WAVE then activates Arp2/3 (important in actin organisation)

31
Q

Explain how Cdc42 causes actin polymerisation/organisation.

A

Cdc42 binds to WASP

WASP activates Arp2/3 (important in actin organisation)

32
Q

Which small GTPases are involved in lamellipodia protrusion?

A

Rac

33
Q

Which small GTPases are involved in focal adhesion assembly?

A

Rac + Rho

34
Q

Which small GTPases are involved in contraction?

A

Rho (assembles stress fibres, important for contraction)

35
Q

What molecules are involved in all types of tumour cell migration? (Individual and collective)

A

Integrins

Proteases

36
Q

What molecules are only involved in collective tumour cell migration?

A

Cadherins

Gap junctions

37
Q

What are the main roles of integrins?

A

Signalling port to connect the cytoskeleton to the ECM

To structurally support the cell

38
Q

What are the 2 types of motility?

A

Hapoptatic: Aimless, non directional movement
Chemotactic: Purposeful, polar movement

39
Q

Describe the different filament organisations and structures found in motile cells

A

Filopodium: Bundle of parallel filaments
Lamellipodium: Branched + cross linked filaments
Stress fibres: Antiparallel contractile structures that form focal adhesions

40
Q

What are the 2 ways in which G-actin can be remodelled?

A

Nucleating

Sequestering

41
Q

Which molecule helps contraction of cells?

A

Myosin

42
Q

How are the Rho subfamily of small GTPases activated?

A

By receptor tyrosine kinase, adhesion receptors + signal transduction pathways

43
Q

What is the importance of Cdc42 in cell migration?

A

Generation of filopodia to sense appropriate direction of movement
Receptors to chemotractants need Cdc42 to transduce signalling that occurs in the cell
Important for actin polymerisation as with Rac control Arp2/3 complex formation

YR2: MCD Cancer (18 decks)

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