11: Invasion Flashcards
What are the steps of tumour progression?
- Homeostasis
- Genetic alterations
- Hyper-proliferation
- De-differentiation
- Invasion
What are the steps of tumour progression?
- Homeostasis (normal)
- Genetic alterations
- Hyper-proliferation (BENIGN tumour)
- De-differentiation - loss of cell-cell contact and POLARITY
- Invasion - increased motility, cleavage of ECM proteins, cells break into basement membrane = MALIGNANT tumour
What are the steps of cell movement?
- Disassembly
- Nucleation
- Polymerisation
- Branching/severing/capping/bundling
- Gel/sol transition
- Attachment to ECM
- Contraction
- Detachment
What structures are used for motility?
Filopodia - Finger-like projections rich in actin
Lamellipodia - sheet-like protrusions
What structures are used for motility?
Filopodia - Finger-like projections, PARALLEL filaments
Lamellipodia - branched and crosslinked sheet-like protrusions
What is the limiting step in actin polymerisation?
NUCLEATION - Occurs at the minus end
Requires high energy AND Arp2/3 complex
Formation of trimer key in initiating polymerisation
What is the limiting step in actin polymerisation?
NUCLEATION - Occurs at the minus end
Requires high energy AND Arp complex
Formation of trimer key in initiating polymerisation
Explain elongation
Occurs at PLUS end
REQUIRES ENERGY
Actin monomers can form complexes with either:
PROFILIN (monomer-binding) - promotes polymerisation
THYMOSIN (sequestering) - inhibits polymerisation
What can happen to actin once it has been severed?
It can be recycled into monomers and join the plus end
It can form a cap and join plus end
Severed filament could also grow as its own
Annealing = severed filaments joined together again
What can happen to actin once it has been severed?
It can be recycled into monomers and join the plus end
It can form a cap (Barbed-end capping)
Severed filament could also grow as its own
Annealing = severed filaments joined together again
What happens after elongation?
Cross-linking and bundling
Done by different proteins according to what shape is needed
Explain branching - what protein is responsible?
Occurs at 70 degree angle
Branching protein = ARP complex
What is gel-sol transition?
If cells need to protrude/move forward they need to break rigid cortex and allow the cytoplasm to flow
Gel = rigid Sol = can flow
This is done by actin filament severing
How is lamella protrusion controlled?
Severing, disassembly, polymerisation, branching, capping, contraction pulls cell forward
How is filopodia controlled?
Polymerisation (only at tip), bundling, cross-linking