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MCD: Cancer > Invasion- regulation of cell migration > Flashcards

Invasion- regulation of cell migration Flashcards

1
Q

What are the steps in tumour progression?

A

Homeostasis
Genetic alterations
Hyperproliferation
Dedifferentiation (disassembly of cell-cell contacts; loss of polarity)
Invasion (increased motility; cleavage of ECM proteins)

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2
Q

What are the 2 broad types of tumour cell migration?

A

Individual

Collective

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3
Q

What is required in individual tumour cell migration?

A

Integrins and proteases

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4
Q

What is required in collective tumour cell migration?

A

Cadherins and gap junctions

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5
Q

Give 2 individual tumour cell migration strategies.

A

Ameoboid

Mesenchymal (single cells)

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6
Q

Give 3 collective tumour cell migration strategies.

A

Mesenchymal (chains)
Clusters/cohorts
Multicellular strands/sheets

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7
Q

What tumour types adopt an ameoboid migration strategy?

A

Lymphoma
Leukaemia
SCLC

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8
Q

What tumour cell types adopt a mesenchymal (single cell) migration strategy?

A

Fibrosarcoma
Glioblastoma
Anaplastic tumours

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9
Q

What tumour cell types adopt a cluster/cohort migration strategy?

A

Epithelial cancer

Melanoma

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10
Q

What tumour cell types adopt a multicellular strand/sheet migration strategy?

A

Epithelial cancer

Vascular tumours

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11
Q

What can stimulate cells to move?

A

Organogenesis and morphogenesis
Wounding
Growth factors/chemoattractants
Dedifferentiation (tumours)

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12
Q

How do cells know where to move to?

A

Directionality (polarity)

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13
Q

How do cell know when to stop moving?

A

Contact inhibition motility

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14
Q

How do cells move?

A

Engage into specialised structures, e.g. focal adhesions, lamellae, filopodium.

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15
Q

What are filopodia?

A

Structures used for cell motility.
Finger-like protrusions rich in actin filaments.
Bundle of parallel filaments.

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16
Q

What are lamellipodia?

A

Structures used for cell motility.
Sheet-like protrusions rich in actin filaments.
Branched and cross-linked filaments.

17
Q

Why is control of cell movement necessary?

A

Needed within a cell to coordinate what is happening in different parts.
Regulate adhesion/release of cell-ECM receptors.
Needed from outside to respond to external influences- sensors, directionality.

18
Q

What are the 2 types of cell motility?

A

Hapoptatic

Chemotatic

19
Q

What are the stages in cell motility?

A

Extension
Adhesion
Translocation
Deadhesion

20
Q

What are stress fibres?

A

Antiparallel contractile structures.

21
Q

What are the 2 types of actin?

A

G-actin (small soluble subunits)

F-actin (large filamentous polymer)

22
Q

How can G-actin be remodelled?

A

Sequestering
Nucleating
Into F-actin

23
Q

How can F-actin be remodelled?

A 
Bundling
Motor proteins
Side-binding
Capping
Cross-linking
Severing
Into G-actin
24
Q

What is nucleation (in cell motility)?

A

Rate-limiting step in actin dynamics.

Formation of trimers to initiate polymerisation.

25
Q

What is elongation (in cell motility)?

A

Profilin competes with thymosin for binding to actin monomers and promotes assembly.

26
Q

List capping proteins that cap the + end.

A

Cap Z
Gelsolin
Fragmin/severin

27
Q

List capping proteins that cap the - end.

A

Tropomodulin

Arp complex

28
Q

What is the role of capping proteins in cell motility?

A

Regulate elongation.

29
Q

List severing proteins.

A

Gelsolin
ADF/cofilin
Fragmin/severin

30
Q

What is the role of severing in cell motility?

A

In a severed population, actin filaments grow and shrink more rapidly than in an unsevered population.

31
Q

List proteins involved in cross-linking and bundling of actin filaments.

A 
Alpha-actinin
Fimbrin
Filamin
Spectrin
Villin
Vinculin
32
Q

What is the main branching protein involved in cell motility?

A

Arp complex

Creates 70 degree angle between actin filaments.

33
Q

What is gel-sol transition in cell motility?

A

Transition from gel (rigid) to sol (can flow) by actin filament severing.

34
Q

What actions are required in regulation of filopodia extension?

A

Actin polymerisation
Bundling
Cross-linking

35
Q

What are the signalling mechanisms that regulate the actin cytoskeleton?

A

Ion flux changes (i.e. intracellular calcium).
Phosphoinositide signalling (phospholipid binding).
Kinases/phosphatases (phosphorylation cytoskeletal proteins).
Signalling cascades via small GTPases.

36
Q

How is the actin cytoskeleton controlled by small G proteins?

A

Rho subfamily of small GTPases belongs to Ras super-family.
Participate in a variety of cytoskeletal processes.
G proteins activated by receptor tyrosine kinase, adhesion receptors and signal transduction pathways.
Expression levels up-regulated in different human tumours.

37
Q

What are the roles of Rac in cell motility?

A

Involved in actin polymerisation and branching of the lamellipodium (extension).
Involved in focal adhesion assembly with Rho (adhesion).

38
Q

What are the roles of Rho in cell motility?

A

Involved in focal adhesion assembly with Rac (adhesion).
Involved in stress fibres, tension and contraction (translocation).
Deadhesion.

39
Q

What are the role of Cdc42 in cell motility?

A

Exploratory processes of filopodia
Polarised motility
Actin polymerisation

MCD: Cancer (17 decks)

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