Invasion Of Cancer

Question 1

What is the name given to cell movement without purpose?

Answer 1

Hapoptatic

Question 2

What is the name given to purposeful movement of cells?

Answer 2

Chemotatic

Question 3

Briefly outline cell motility

Answer 3

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

Question 4

What do you call actin monomers and polymers?

Answer 4

Monomer - G actin

Polymer - F actin

Question 5

Describe the three types of actin filament organisation

Answer 5

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

Question 6

List the type of F actin filaments organisation

Answer 6

Bundle
Motor proteins
Side Binding
Capping
Cross linking
Severing

Question 7

What is the rate limiting step in polymerisation?

Answer 7

Nucleation of G protein

Question 8

Which proteins facilitate nucleation of G actin?

Answer 8

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

Question 9

Which protein brings actin to ARP?

Answer 9

Profilin

Question 10

Which protein inhibits actin nucleation?

Answer 10

Thymosin

Question 11

Which capping proteins bind at the plus end?

Answer 11

Cap Z
Gelsolin
Fragmin/severin

Question 12

Which capping proteins bind at the minus end?

Answer 12

Tropomodulin

ARP complex

Question 13

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

Answer 13

Gelsolin
ADF/cofilin
Fragmin/severin

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

Question 14

Which proteins cross link the filaments across short distances?

Answer 14

Fascin

Question 15

Which proteins cross link the filaments as a dimer?

Answer 15

Alpha actin

Question 16

Which proteins cross link the filaments in different angles?

Answer 16

Spectrin
Filamin
Dystrophin

Question 17

Which proteins help actin polymers form bundles?

Answer 17

Vilin

Vinculin

Question 18

Which proteins cross link the filaments across long distances?

Answer 18

Fimbrin

Question 19

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

Answer 19

Arp complex, at 70°

Question 20

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

Answer 20

They break some bonds in the cross linking using gelsolin

Question 21

What stimulates cell movement?

Answer 21

Organogenesis/morphogenesis
Wounding
Growth factors/chemo attractants
De differentiation

Question 22

Describe how the cell binds to the ECM

Answer 22

Via focal adhesions:

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

Question 23

What needs to happen to actin during lamellipodium extension?

Answer 23

Polymerisation of actin:
Disassembly
Nucleation
Branching
Severing
Capping
Bundling

Question 24

When does gelsol transition occur?

Answer 24

During translocation?

Question 25

Describe the formation of lamellipodia protrusions

Answer 25

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

Question 26

Describe filopodia formation

Answer 26

Monomers added to the front Actin polymerisation Bundling Cross linking

Question 27

Give examples of other cytoskeletal actin organisation

Answer 27

``` Cilia Micro villi Stereocilia Filopodia Lamellipodia ```

Question 28

Which signalling mechanisms regulate actin cytoskeleton?

Answer 28

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

Question 29

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

Answer 29

Rho subfamily, belongs to the Ras superfamily

Question 30

Which family members of Rho and what do they regulate?

Answer 30

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

Question 31

Describe the activation of Rho GTPases

Answer 31

Active when bound to GTP

Question 32

Name some downstream proteins regulated by the cdc42

Answer 32

Wave | Arp2/3

Question 33

Name some downstream proteins regulated by the Rac

Answer 33

Wasp | Arp2/3

Question 34

Name some downstream proteins regulated by the Cdc42 and Rac

Answer 34

Cofilin | Profilin

Question 35

How is the Rho family implicated in cancer?

Answer 35

Point mutations | Up regulation

Question 36

What activates Rho?

Answer 36

Receptor tyrosine kinases Adhesion receptors Signal transduction pathways

Question 37

Describe how a cell moves from being benign to malignant?

Answer 37

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

Question 38

List physiological movement of cells which are mimicked by cancer metastasis

Answer 38

Mammary gland growth Vascular growth Wound healing

Question 39

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

Answer 39

Individual cell migration - requires integrins and proteases Collective cell migration - requires cadherins and gap junctions

Question 40

What gives a cell direction?

Answer 40

Polarity

Question 41

What tells a cell when to stop moving?

Answer 41

Cell cell contact

Question 42

Describe how filopodia form adhesions and move.

Answer 42

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

Question 43

Nucleation of an actin filament involves?

Answer 43

Arp2, Arp3 and G-actin

Question 44

Which molecules are involved in elongation?

Answer 44

Profilin and thymosin are involved in elongation.

Question 45

Which molecules control the rate of actin growth?

Answer 45

CapZ and gelsolin control the rate of growth.