Invasion- regulation of cell migration

Question 1

What are the steps in tumour progression?

Answer 1

Homeostasis
Genetic alterations
Hyperproliferation
Dedifferentiation (disassembly of cell-cell contacts; loss of polarity)
Invasion (increased motility; cleavage of ECM proteins)

Question 2

What are the 2 broad types of tumour cell migration?

Answer 2

Individual

Collective

Question 3

What is required in individual tumour cell migration?

Answer 3

Integrins and proteases

Question 4

What is required in collective tumour cell migration?

Answer 4

Cadherins and gap junctions

Question 5

Give 2 individual tumour cell migration strategies.

Answer 5

Ameoboid

Mesenchymal (single cells)

Question 6

Give 3 collective tumour cell migration strategies.

Answer 6

Mesenchymal (chains)
Clusters/cohorts
Multicellular strands/sheets

Question 7

What tumour types adopt an ameoboid migration strategy?

Answer 7

Lymphoma
Leukaemia
SCLC

Question 8

What tumour cell types adopt a mesenchymal (single cell) migration strategy?

Answer 8

Fibrosarcoma
Glioblastoma
Anaplastic tumours

Question 9

What tumour cell types adopt a cluster/cohort migration strategy?

Answer 9

Epithelial cancer

Melanoma

Question 10

What tumour cell types adopt a multicellular strand/sheet migration strategy?

Answer 10

Epithelial cancer

Vascular tumours

Question 11

What can stimulate cells to move?

Answer 11

Organogenesis and morphogenesis
Wounding
Growth factors/chemoattractants
Dedifferentiation (tumours)

Question 12

How do cells know where to move to?

Answer 12

Directionality (polarity)

Question 13

How do cell know when to stop moving?

Answer 13

Contact inhibition motility

Question 14

How do cells move?

Answer 14

Engage into specialised structures, e.g. focal adhesions, lamellae, filopodium.

Question 15

What are filopodia?

Answer 15

Structures used for cell motility.
Finger-like protrusions rich in actin filaments.
Bundle of parallel filaments.

Question 16

What are lamellipodia?

Answer 16

Structures used for cell motility.
Sheet-like protrusions rich in actin filaments.
Branched and cross-linked filaments.

Question 17

Why is control of cell movement necessary?

Answer 17

Needed within a cell to coordinate what is happening in different parts.
Regulate adhesion/release of cell-ECM receptors.
Needed from outside to respond to external influences- sensors, directionality.

Question 18

What are the 2 types of cell motility?

Answer 18

Hapoptatic

Chemotatic

Question 19

What are the stages in cell motility?

Answer 19

Extension
Adhesion
Translocation
Deadhesion

Question 20

What are stress fibres?

Answer 20

Antiparallel contractile structures.

Question 21

What are the 2 types of actin?

Answer 21

G-actin (small soluble subunits)

F-actin (large filamentous polymer)

Question 22

How can G-actin be remodelled?

Answer 22

Sequestering
Nucleating
Into F-actin

Question 23

How can F-actin be remodelled?

Answer 23

Bundling
Motor proteins
Side-binding
Capping
Cross-linking
Severing
Into G-actin

Question 24

What is nucleation (in cell motility)?

Answer 24

Rate-limiting step in actin dynamics.

Formation of trimers to initiate polymerisation.

Question 25

What is elongation (in cell motility)?

Answer 25

Profilin competes with thymosin for binding to actin monomers and promotes assembly.

Question 26

List capping proteins that cap the + end.

Answer 26

Cap Z Gelsolin Fragmin/severin

Question 27

List capping proteins that cap the - end.

Answer 27

Tropomodulin | Arp complex

Question 28

What is the role of capping proteins in cell motility?

Answer 28

Regulate elongation.

Question 29

List severing proteins.

Answer 29

Gelsolin ADF/cofilin Fragmin/severin

Question 30

What is the role of severing in cell motility?

Answer 30

In a severed population, actin filaments grow and shrink more rapidly than in an unsevered population.

Question 31

List proteins involved in cross-linking and bundling of actin filaments.

Answer 31

``` Alpha-actinin Fimbrin Filamin Spectrin Villin Vinculin ```

Question 32

What is the main branching protein involved in cell motility?

Answer 32

Arp complex | Creates 70 degree angle between actin filaments.

Question 33

What is gel-sol transition in cell motility?

Answer 33

Transition from gel (rigid) to sol (can flow) by actin filament severing.

Question 34

What actions are required in regulation of filopodia extension?

Answer 34

Actin polymerisation Bundling Cross-linking

Question 35

What are the signalling mechanisms that regulate the actin cytoskeleton?

Answer 35

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

Question 36

How is the actin cytoskeleton controlled by small G proteins?

Answer 36

Rho subfamily of small GTPases belongs to Ras super-family. Participate in a variety of cytoskeletal processes. G proteins activated by receptor tyrosine kinase, adhesion receptors and signal transduction pathways. Expression levels up-regulated in different human tumours.

Question 37

What are the roles of Rac in cell motility?

Answer 37

Involved in actin polymerisation and branching of the lamellipodium (extension). Involved in focal adhesion assembly with Rho (adhesion).

Question 38

What are the roles of Rho in cell motility?

Answer 38

Involved in focal adhesion assembly with Rac (adhesion). Involved in stress fibres, tension and contraction (translocation). Deadhesion.

Question 39

What are the role of Cdc42 in cell motility?

Answer 39

Exploratory processes of filopodia Polarised motility Actin polymerisation