Invasion Of Cancer Flashcards

1
Q

What is the name given to cell movement without purpose?

A

Hapoptatic

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2
Q

What is the name given to purposeful movement of cells?

A

Chemotatic

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3
Q

Briefly outline cell motility

A
Focal adhesions
Extension using lamellipodia
Adhesion
Contraction and translocation
Deadhesion at the back
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4
Q

What do you call actin monomers and polymers?

A

Monomer - G actin

Polymer - F actin

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5
Q

Describe the three types of actin filament organisation

A

Filopodium - parallel branches
Lamellipodium - cross linked, sheet like protrusions
Stress fibres - anti parallel #, allows cell to contract

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6
Q

List the type of F actin filaments organisation

A
Bundle
Motor proteins
Side Binding
Capping
Cross linking
Severing
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7
Q

What is the rate limiting step in polymerisation?

A

Nucleation of G protein

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8
Q

Which proteins facilitate nucleation of G actin?

A

Arp 2 and 3 (ARP complex) create a timer of actin

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9
Q

Which protein brings actin to ARP?

A

Profilin

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10
Q

Which protein inhibits actin nucleation?

A

Thymosin

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11
Q

Which capping proteins bind at the plus end?

A

Cap Z
Gelsolin
Fragmin/severin

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12
Q

Which capping proteins bind at the minus end?

A

Tropomodulin

ARP complex

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13
Q

Which proteins sever the actin polymer and what effect does this have?

A

Gelsolin
ADF/cofilin
Fragmin/severin

The smaller you cut it, the more quickly you can grow it.

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14
Q

Which proteins cross link the filaments across short distances?

A

Fascin

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15
Q

Which proteins cross link the filaments as a dimer?

A

Alpha actin

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16
Q

Which proteins cross link the filaments in different angles?

A

Spectrin
Filamin
Dystrophin

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17
Q

Which proteins help actin polymers form bundles?

A

Vilin

Vinculin

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18
Q

Which proteins cross link the filaments across long distances?

A

Fimbrin

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19
Q

Which proteins enable branching of actin polymers and at which particular angle?

A

Arp complex, at 70°

20
Q

How do cells enable their membrane to be more flexible for movement and using which protein?

A

They break some bonds in the cross linking using gelsolin

21
Q

What stimulates cell movement?

A

Organogenesis/morphogenesis
Wounding
Growth factors/chemo attractants
De differentiation

22
Q

Describe how the cell binds to the ECM

A

Via focal adhesions:

Actin cytoskeleton binds to a plaque, which binds to a transmembrane integrin which binds to the ECM

23
Q

What needs to happen to actin during lamellipodium extension?

A
Polymerisation of actin:
Disassembly
Nucleation
Branching
Severing
Capping
Bundling
24
Q

When does gelsol transition occur?

A

During translocation?

25
Q

Describe the formation of lamellipodia protrusions

A

Assembly of actin filaments at forefront
Capping and severing at back
Monomers moved to front
New branches formed at front by ARP

26
Q

Describe filopodia formation

A

Monomers added to the front
Actin polymerisation
Bundling
Cross linking

27
Q

Give examples of other cytoskeletal actin organisation

A
Cilia
Micro villi
Stereocilia
Filopodia
Lamellipodia
28
Q

Which signalling mechanisms regulate actin cytoskeleton?

A

Ion flux changes (intracellular calcium)
Phosphoinositide signalling (PI3K) - phospholipid burning
Kinases/phosphatases (phosphorylation of cytoskeletal proteins)
GTPases

29
Q

Which small G proteins control actin cytoskeleton and which family do they belong to?

A

Rho subfamily, belongs to the Ras superfamily

30
Q

Which family members of Rho and what do they regulate?

A

Cdc42 - master regulator of filopodia
Rac - lamellipodia
Rho - stress fibres

31
Q

Describe the activation of Rho GTPases

A

Active when bound to GTP

32
Q

Name some downstream proteins regulated by the cdc42

A

Wave

Arp2/3

33
Q

Name some downstream proteins regulated by the Rac

A

Wasp

Arp2/3

34
Q

Name some downstream proteins regulated by the Cdc42 and Rac

A

Cofilin

Profilin

35
Q

How is the Rho family implicated in cancer?

A

Point mutations

Up regulation

36
Q

What activates Rho?

A

Receptor tyrosine kinases
Adhesion receptors
Signal transduction pathways

37
Q

Describe how a cell moves from being benign to malignant?

A
It becomes dedifferentiated
Loss of polarity
Loss of cell cell junctions
Up regulation of cytoskeletal regulation and motility machinery
Breakaway from basement membrane
38
Q

List physiological movement of cells which are mimicked by cancer metastasis

A

Mammary gland growth
Vascular growth
Wound healing

39
Q

What are the two types of cell migration and what do they require?

A

Individual cell migration - requires integrins and proteases

Collective cell migration - requires cadherins and gap junctions

40
Q

What gives a cell direction?

A

Polarity

41
Q

What tells a cell when to stop moving?

A

Cell cell contact

42
Q

Describe how filopodia form adhesions and move.

A

Filopodia are fingerlike projections found on the leading edge of migrating cells. They form focal adhesions to the substratum and are pulled forward by treadmilling of actin fibre

43
Q

Nucleation of an actin filament involves?

A

Arp2, Arp3 and G-actin

44
Q

Which molecules are involved in elongation?

A

Profilin and thymosin are involved in elongation.

45
Q

Which molecules control the rate of actin growth?

A

CapZ and gelsolin control the rate of growth.