CANCER- regulation of cell migration Flashcards
What are the molecular mechanisms that regulate
motility?
microfilaments
regulation of actin dynamics
cytoskeletal proteins
signalling proteins
what are the steps of tumour progression?
homeostasis
genetic alterations
hyper proliferation
de differentiation
- Disassembly of cell-cell contacts.
- Loss of cell polarity.
invasion
- Increased motility.
- Cleavage of ECM proteins.
what are the two types of individual cell migration?
o Amoeboid – e.g. lymphomas.
o Mesenchymal (single) – e.g. Fibrosarcoma.
what are they different types of collective cell migration?
o Mesenchymal (chains) – e.g. Fibrosarcoma.
o Cluster/cohorts – e.g. Epithelial cancers.
o Multicellular strands/sheets – e.g. Epithelial cancers.
what does EGF do to tumours and what family is it a member of?
increases motility, proliferation, survival and differentiation.
member of the ErbB family of receptor tyrosine kinases
what are some stimuli of cell movement?
organogenesis and morphogenesis
wounding
growth factors/ chemoattractants
dedifferentiation (tumours)
how do the cells know when to stop?
contact inhibition
how do the cells mobilise?
For motility, the cell uses:
o Filopodia – finger-like projections rich in actin filaments.
- -> A bundle of parallel filaments.
- -> actin or vinculin
o Lamellipodia – sheet-like protrusions rich in actin filaments.
–> Branched and crosslinked filaments
the cells can remodel the cytoskeleton
what are the two different types of movement and what is the difference
hapoptatic- just a general movement
chemotatic- there is a purpose for the movement
what are the different stages of movement?
- extension
- adhesion
- translocation
- de-adhesion
what different states is actin found in?
G-actin- small soluble sub units
F-actin- large filamentous polymer
what is nucleation?
two molecules that mimic actin come together with an actin molecule to form a trimer which initiate polymerisation
§ Attachment of the actin to the cell inner membrane.
§ ARP proteins form a complex and bind to actin monomers to create a nucleated actin filament (ARPs bind to the minus end).
§ This is the limiting step in actin dynamics.
what happens in elongation?
§ Profilin facilitates actin monomer binding to the actin filament.
§ Thymosin reduces actin monomer binding by sequestering the free monomers so they are not available to bind to the actin filament.
what is capping?
give some examoles of capping proteins
addition of a capping molecule (to + or – end) to limit elongation.
o Plus-end caps – Cap Z, Gelsolin, Fragmin/Severin.
o Minus-end caps – Tropomodulin, Arp complex.
what is severing?
give some examples of severing proteins
breaking up actin filaments:
o Unsevered actin filaments grow/shrink slowly.
o Severed populations grow/shrink more rapidly
eg. gelsolin
ADF/cofilin
fragmin/severin
