Cancer 8:Invasion - regualtion of cell migration Flashcards
Outline what occurs when a tumour metastasizes
- 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
What 4 types of tumour cell migration strategy are there?
- ameoboid
- mesenchymal (single cells and chains)
- cluster/cohorts
- multicellular strands/sheets
What tumour type uses ameoboid as its migration strategy?
- lymphoma
- leukaemia
- SCLC
What tumour type uses mesenchymal as its migration strategy?
- fibrosarcoma
- glioblastoma
- anaplastic tumours
What tumour type uses cluster/cohort as its migration strategy?
- epithelial cancer
- melanoma
What tumour type uses multicellular strands as its migration strategy?
- epithelial cancer
- vascular tumours
What are the FOUR stimuli for a cell to move?
- organogenesis and morphogenesis
- wounding
- growth factors/ chemoattractants
- dedifferentiation
What determines the direction of cell movement and when it stops?
- the direction is determined by the polarity of the cell and it will stop moving by contact-inhibition motility
Which parts of the cell attach to ECM proteins?
- focal adhesions
- filamentous actin
What are filopodia?
finger-like protrusions rich in actin filaments
What are lamellipodia?
sheet-like protrusions rich in actin filaments
Why is control needed for cell movement?
- within a cell to coordinate what is happening in different parts
- regulate adhesion/release of cell-extracellular matrix receptors
- to respond to external influences
WHat are the 4 basic steps of cell motility?
- extension
- adhesion
- translocation
- de-adhesion
How does G-actin depolarize the cell?
- 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
How does nucleation occur?
- ARP complex binds with actin monomers to form a nucleated actin filament
- the formation of trimers initiates polymerization
How does elongation occur?
profilin competes with thymosin for binding to actin monomers and promotes assembly
How does capping occur?
capping proteins inhibit growth in one direction
positive end:
- cap Z
- gelsolin
- fragmin/severin
negative end:
- tropomodulin
- arp complex
Why is severing done and how does it occur?
- 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
By what proteins does cross-linking and bundling occur?
alpha actinin fimbrin filamin spectrin villin vinculin
What is the branching protein?
ARP complex
-branching always occurs at 70 degrees
What does gel-sol transition mean and how does it occur?
- actin filament severing
- the cytoskeleton goes from rigid to be able to flow
What actin activities does lamellae protrusion involve?
-polymerization, disassembly, branching, capping
What actin activites does filopodia involve?
- actin polymerization
- bundling
- crosslinking
What are the FOUR signalling mechanisms that regulate the actin cytoskeleton?
- ion flux changes
- phosphoinositide signalling
- kinases/phosphatases
- signalling cascades via small GTPases
