Invasion – Regulation of Cell Motility Flashcards Preview

Y2 MCD - Cancer - Laz > Invasion – Regulation of Cell Motility > Flashcards

Flashcards in Invasion – Regulation of Cell Motility Deck (35)
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1

What are the changes that occur in the cells that occur during tumour progression?

Genetic alterations lead to hyperproliferation, disassembly of cell-cell contacts, loss of polarity, increased motility and cleavage of ECM proteins

2

What are the different types of tumour cell migration?

Single cell migration (ameboid)
Mesenchymal single cells
Mesenchymal chains
Clusters/cohorts
Multicellular strands/sheets

3

What physiological phenomena does tumour migration mimic?

Morphogenesis e.g. angiogenesis

4

What did a comparison of the expression profile of invasive cells vs primary tumours show to be upregulated in invasive cells?

Cytoskeleton regulation
Motility machinery

5

What makes normal migrating cells stop moving?

Contact inhibition of locomotion

6

How are tumour cells different in this aspect?

They lose contact inhibition of locomotion so they can multilayer

7

What is another term for ECM proteins?

Substratum

8

What are filopodia?

Finger-like protrusions that are rich in actin filaments
They sense the local environment

9

What are lamellipodia?

Sheet-like protrusions that are rich in actin filaments

10

What are the four main stages of cell movement?

Extension
Adhesion
Translocation
De-adhesion

11

What are the attachments between the cell and the surface that it is moving along called?

Focal adhesions

12

What are the monomers of actin filaments?

G-actin

13

Describe the polarity of acting filaments.

They have a plus end and a minus end
The monomers preferentially get added on at the plus end

14

What protein complex is important in initiating polymerisation?

Arp2/3
This forms a trimer with actin and is good at initiating polymerisation

15

What is the limiting step in actin dynamics?

Formation of Arp2/3-actin trimers to initiate polymerisation

16

State two proteins that bind to free G-actin and describe how they affect elongation.

Promote elongation – profilin (these deliver the G-actin to the growing filament)
Sequesters G-actin beta–4 thymosin ADF, cofilin

17

Name some + end capping proteins.

CapZ
Gelsolin
Fragmin/severin

18

Name some – end capping proteins.

Tropomodulin
Arp2/3

19

Name some severing proteins.

Gelsolin ADF
Framin/severin
Cofilin

20

What are the features of the actin filaments in severed populations?

Actin filaments can grow and shrink more rapidly

21

What can happen to single filaments of actin to improve their structural integrity?

They can be bundled or cross-linked

22

Name some proteins involved in these processes.

Alpha-actinin
Fimbrin
Filamin
Spectrin
Villin
Vinculin

23

Which protein allows branching of the actin filaments?

Arp2/3

24

At what angle do they branch?

70 degrees

25

Summarise the actions of Arp2/3.

They initiate nucleation
They cap filaments
They cause branching

26

Describe what causes the gel-sol transition.

The actin filaments can be severed to make the cell more fluid

27

Describe the actin processes that take place during the protusion of lamellipodia.

There is polymerisation, disassembly, branching and capping
There is net filament assembly at the leading edge

28

Describe the actin processes that take place during the formation of filopodia.

Actin polymerisation
Bundling and cross-linking
(NO branching)
As soon as the finger wants to retract it will collapse at the base

29

State four signalling mechanisms that regulate the actin cytoskeleton.

Ion flux changes
Phosphoinositide signalling
Kinases/phosphatases
Small GTPases

30

What are the three most important small GTPases in terms of the actin cytoskeleton and what does activation of each cause?

Cdc42 – filopodia
Rac – lamellipodia
Rho – stress fibres
NOTE: these are all part of the Rho family