Cancer 8:Invasion - regualtion of cell migration

Question 1

Outline what occurs when a tumour metastasizes

Answer 1

• epithelial cells in primary tumours are bound tightly together
• metastatic tumour cells become mobile mesenchyme-type cells and enter the bloodstream
• metastatic cells then travel through the bloodstream to a new location and they then exit the circulation, invading a new organ

Question 2

What 4 types of tumour cell migration strategy are there?

Answer 2

• ameoboid
• mesenchymal (single cells and chains)
• cluster/cohorts
• multicellular strands/sheets

Question 3

What tumour type uses ameoboid as its migration strategy?

Answer 3

• lymphoma
• leukaemia
• SCLC

Question 4

What tumour type uses mesenchymal as its migration strategy?

Answer 4

• fibrosarcoma
• glioblastoma
• anaplastic tumours

Question 5

What tumour type uses cluster/cohort as its migration strategy?

Answer 5

• epithelial cancer

- melanoma

Question 6

What tumour type uses multicellular strands as its migration strategy?

Answer 6

• epithelial cancer

- vascular tumours

Question 7

What are the FOUR stimuli for a cell to move?

Answer 7

• organogenesis and morphogenesis
• wounding
• growth factors/ chemoattractants
• dedifferentiation

Question 8

What determines the direction of cell movement and when it stops?

Answer 8

• the direction is determined by the polarity of the cell and it will stop moving by contact-inhibition motility

Question 9

Which parts of the cell attach to ECM proteins?

Answer 9

• focal adhesions

- filamentous actin

Question 10

What are filopodia?

Answer 10

finger-like protrusions rich in actin filaments

Question 11

What are lamellipodia?

Answer 11

sheet-like protrusions rich in actin filaments

Question 12

Why is control needed for cell movement?

Answer 12

• within a cell to coordinate what is happening in different parts
• regulate adhesion/release of cell-extracellular matrix receptors
• to respond to external influences

Question 13

WHat are the 4 basic steps of cell motility?

Answer 13

• extension
• adhesion
• translocation
• de-adhesion

Question 14

How does G-actin depolarize the cell?

Answer 14

• the cell receives a signal such as a nutrient source
• F-actin rapidly disassembles and there is a rapid diffusion of the subunits
• then from the g-actin the filaments reassemble at a new site
• depolarising the cell at this point and causing it to move in that direction

Question 15

How does nucleation occur?

Answer 15

• ARP complex binds with actin monomers to form a nucleated actin filament
• the formation of trimers initiates polymerization

Question 16

How does elongation occur?

Answer 16

profilin competes with thymosin for binding to actin monomers and promotes assembly

Question 17

How does capping occur?

Answer 17

capping proteins inhibit growth in one direction

positive end:

• cap Z
• gelsolin
• fragmin/severin

negative end:

• tropomodulin
• arp complex

Question 18

Why is severing done and how does it occur?

Answer 18

• in unsevered population actin filaments grow and shrink relatively slowly BUT in severed populations actin filaments grow and shrink more rapidly

SEVERING PROTEINS:

• gelsolin
• ADF/cofilin
• fragmin/severin

Question 19

By what proteins does cross-linking and bundling occur?

Answer 19

alpha actinin
fimbrin
filamin
spectrin
villin 
vinculin

Question 20

What is the branching protein?

Answer 20

ARP complex

-branching always occurs at 70 degrees

Question 21

What does gel-sol transition mean and how does it occur?

Answer 21

• actin filament severing

- the cytoskeleton goes from rigid to be able to flow

Question 22

What actin activities does lamellae protrusion involve?

Answer 22

-polymerization, disassembly, branching, capping

Question 23

What actin activites does filopodia involve?

Answer 23

• actin polymerization
• bundling
• crosslinking

Question 24

What are the FOUR signalling mechanisms that regulate the actin cytoskeleton?

Answer 24

• ion flux changes
• phosphoinositide signalling
• kinases/phosphatases
• signalling cascades via small GTPases

Question 25

How does Rho help control the actin cytoskeleton?

Answer 25

• it is activated by receptor tyrosine kinase, adhesion receptors and signal transduction pathways
• when Rho is linked to GTP it leads to a response
• expression levels up-regulated in different human tumours

Question 26

What occurs when you activate Cdc42, Rac or Rho

Answer 26

• Cdc42 activates filopodia
• Rac activates lamellipodia
• Pho activates stress fibers