11: Invasion Flashcards

1
Q

What are the steps of tumour progression?

A
  1. Homeostasis
  2. Genetic alterations
  3. Hyper-proliferation
  4. De-differentiation
  5. Invasion
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2
Q

What are the steps of tumour progression?

A
  1. Homeostasis (normal)
  2. Genetic alterations
  3. Hyper-proliferation (BENIGN tumour)
  4. De-differentiation - loss of cell-cell contact and POLARITY
  5. Invasion - increased motility, cleavage of ECM proteins, cells break into basement membrane = MALIGNANT tumour
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3
Q

What are the steps of cell movement?

A
  • Disassembly
  • Nucleation
  • Polymerisation
  • Branching/severing/capping/bundling
  • Gel/sol transition
  • Attachment to ECM
  • Contraction
  • Detachment
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4
Q

What structures are used for motility?

A

Filopodia - Finger-like projections rich in actin

Lamellipodia - sheet-like protrusions

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5
Q

What structures are used for motility?

A

Filopodia - Finger-like projections, PARALLEL filaments

Lamellipodia - branched and crosslinked sheet-like protrusions

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6
Q

What is the limiting step in actin polymerisation?

A

NUCLEATION - Occurs at the minus end
Requires high energy AND Arp2/3 complex
Formation of trimer key in initiating polymerisation

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7
Q

What is the limiting step in actin polymerisation?

A

NUCLEATION - Occurs at the minus end
Requires high energy AND Arp complex
Formation of trimer key in initiating polymerisation

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8
Q

Explain elongation

A

Occurs at PLUS end
REQUIRES ENERGY
Actin monomers can form complexes with either:
PROFILIN (monomer-binding) - promotes polymerisation
THYMOSIN (sequestering) - inhibits polymerisation

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9
Q

What can happen to actin once it has been severed?

A

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

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10
Q

What can happen to actin once it has been severed?

A

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

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11
Q

What happens after elongation?

A

Cross-linking and bundling

Done by different proteins according to what shape is needed

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12
Q

Explain branching - what protein is responsible?

A

Occurs at 70 degree angle

Branching protein = ARP complex

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13
Q

What is gel-sol transition?

A

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

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14
Q

How is lamella protrusion controlled?

A

Severing, disassembly, polymerisation, branching, capping, contraction pulls cell forward

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15
Q

How is filopodia controlled?

A

Polymerisation (only at tip), bundling, cross-linking

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16
Q

What are the types of actin-binding proteins?

A

Monomer-binding: Profilin (polymerisation)
Sequestering: Thymosin (inhibits polymerisation)

Capping: Cap Z/gelsolin/fragmin/severin (+end) or Tropomodulin/Arp complex (-end)

Severing: severin, gelsolin, fragmin
Cross-linking: alpha-actinin, fimbrin
Bundling: filamin, spectrin
Branching: Arp complex

17
Q

Signalling mechanisms that regulate actin cytoskeleton?

A
  1. Ion flux changes
  2. Kinases/phosphatases
  3. Phospholipid binding
  4. Signalling cascades via small GTPases
18
Q

How is actin cytoskeleton controlled by small G proteins?

A

Rho subfamily of small GTPases (within Ras family)
Activated by association with GTP
Activated by receptor TK, adhesion receptors and signal transduction pathways
Expression upregulated in different tumours

19
Q

What does activation of Rho family GTPases in cells result in?

A

Lamellipodia:
Rac -> polymerisation, branching, adhesion
Rho -> Stress fibres, tension, contraction, detachment

Filopodia:
Cdc42 -> polymerisation

20
Q

How does signalling from small GTPases regulate cytoskeleton and motility?

A

They activate actin binding proteins (Arp complexes) via effector proteins

21
Q

How does metastasis occur

A
  1. epithelial cells in primary tumours bound tightly together
  2. Metastatic tumour cells become mobile and enter bloodstream
  3. They then exit the circulation and invade a new organ
  4. Cells lose their motility and form new tumour

Metastasis MIMICS morphogenetic events

22
Q

Types of tumour cell migration?

A

Individual cell migration - Ameoboid (round), mesenchymal (elongated)
Collective migration - clusters, multi-cellular strands

23
Q

Different types of adhesion receptors in tumour cells?

A

Integrins/ proteases - found in ALL types of migration

Cadherins/ gap junctions - clusters and multi-cellular strands ONLY