Invasion- Regulation of Cell Migration Flashcards
what are the 5 stages of tumour progression?
o Homeostasis. o Genetic alterations. o Hyper-proliferation. o De-differentiation o Invasion (benign become malignant)
what happens generally in de-differentiation?
Disassembly of cell-cell contacts.
Loss of cell polarity.
what happens generally in invasion?
Increased motility.
Cleavage of ECM proteins.
what are the two types of cell migration?
Individual cell migration
Collective cell migration
name examples of cells that migrate as individual cells
o Amoeboid – e.g. lymphomas. o Mesenchymal (single) – e.g. Fibrosarcoma.
what are the types of collectives
name example of cells that migrate as collective cells
o Mesenchymal (chains) e.g. Fibrosarcoma
o Cluster/cohorts –
e.g. Epithelial cancers.
o Multicellular strands/sheets –
e.g. Epithelial cancers.
why does collective cell migration still have some cell-cell junctions present?
Collective cell migration requires more coordination to metastasise and so still has some cell-cell junctions
which type of cell migration has a higher malignancy potential?
collective migration compared to the same number of individual cells
what does tumour cell metastasis, i.e. migration, mimic?
normal morphogenic events like branching morphogenesis in the mammary glands or migration of primary glial cells to repair a scratch wound or vascular sprouting
what does tumour cell metastasis compare to normal cell migration?
no clear migration front (unorganised and rapid) and no sense of direction
what genes does EGF have an regulatory effect on?
o Cytoskeleton regulation.
o Motility machinery.
these induce migration
what are the normal stimuli for migration for a cell?
o Organogenesis and morphogenesis
o Wounding
o Growth factor/Chemoattractants
o De-differentiation.
how is direction of travel of the cell determined?
through polarity
how is termination of migration determined?
contact-inhibition when neighbouring cells are recognised and no space is left
how is migration of the cell facilitated?
using specialised structures:
- focal adhesions
- lamellae
- filopodium
what must the cell attach to, to carry out migration?
attach to the ECM via integrins
what are filopodia?
finger-like projections rich in actin filaments.
A bundle of parallel filaments.
what are lamellipodia?
sheet-like protrusions rich in actin filaments.
Branched and crosslinked filaments.
what is the purpose of controlling the process of motility?
o Coordinate happenings inside the cell itself.
o Regulate adhesion/release of cell-ECM.
o To respond to external influences.
what are the two types of motility?
haptotaxis and chemotaxis
Haptotaxis: directional motility or outgrowth of cells
Chemotaxis: gradient developed in soluble fluid
what are the 4 steps of cell migration?
1) extension
2) adhesion
3) translocation
4) de-adhesion
what happens in extension?
focal adhesions exist
what happens in adhesion?
lamellipodium formed and new focal adhesions are created
what happens in translocation?
the cell contracts via actin filaments and moves in a direction
what happens in de-adhesion?
old focal adhesions are broken behind
what enables contraction of the cell?
the polymerisation of actin filaments
how does actin polymerisation help maintain a motion in the cell?
Contraction of Filopodia and Lamellipodia can break old adhesions, allowing the cell to maintain a motion.
what is required to allow assembly and disassembly of actin filaments and therefore movement?
A signal to move could be a nutrient source
Filaments can rapidly disassemble and then reassemble at a new site to move the cell towards this source
how is actin capable of carrying out different functions?
Actin filaments have a polarity- a plus and minus end- on which different proteins can bind.
Depending on the proteins that bind, the actin filaments can carry out different functions.
from what is actin polymerised?
G-actin (small soluble subunits) into F-actin (large filamentous polymer)
there is interconversion between the two so disassembly and assembly happens to travel in the necessary direction
F-actin enables motility
what are the 3 ways in which actin filaments can organise themselves in order to enable motility?
- filopodia (parellel filaments)
- lamellipodia (branched and cross linked filaments)
- stress fibres (antiparallel, contractile structures)
what are the 7 steps of actin remodelling?
1- nucleation 2- elongation 3- capping 4- severing 5- cross linking and bundling 6- branching 7- gel-sol transition