motility final

Question 1

what are steps in tumor progression

Answer 1

Homeostasis

Genetic alterations

Hyper-proliferation (leads to formation of benign tumour)

de-diffferatiation to form malignant tumor

Invasion and metastasis

Question 2

what does de-differntiation involve

Answer 2

cells loose their identity and function as epithelial cells
disassembling cell-cell contacts
losing polarity

Question 3

what does invasion of basement membrane require

Answer 3

cleavage of ECM proteins

increase motility

Question 4

outline how metastasis occurs

Answer 4

metastatic tumour cells become mobile mesenchyme-type cells

these enter blood stream

invade new organ (loose mesechymal properties) and tumour reforms

Question 5

What are the different types of tumour cell migration?

Answer 5

Single cell migration (ameboid) - (lymphoma)

Mesenchymal single cells - (glioblastoma)

Mesenchymal chains - (glioblastoma)

Clusters/cohorts - (epithelial cancer)

Multicellular strands/sheets - (epithelial cancer)

Question 6

What physiological phenomena does tumour migration mimic?

Answer 6

Morphogenesis e.g. angiogenesis

Question 7

how are tumour cells profiled

Answer 7

Tumour cells are inoculated in a mouse, and they form a primary tumour.

GF stimulate migration
primary tumour cells, and invasive cells compared with regards to their expression profile by measuring mRNA levels

Question 8

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

Answer 8

Upregulation of genes involved in:

Cytoskeleton regulation
Motility machinery

Question 9

what are the stimuli for cell movement

Answer 9

organogenesis and morphogenesis

wounding

growth factors/chemoattractants

dedifferentiation (tumours)

Question 10

what instructs cells where to move and when to stop

Answer 10

Where to go? - directionality (polarity)

When to stop?
- contact-inhibition motility

Question 11

How do these cells move?

Answer 11

specialized structures (focal adhesion, lamellae, filopodium)

Question 12

What is another term for ECM proteins?

Answer 12

Substratum

Question 13

what are the 2 types of attachment to substratum

Answer 13

Focal adhesions - site where cell attaches to proteins which make the ECM

Filamentous actin - hooks the focal adhesions to the
cytoskeletons via integrins

Question 14

what are filopodia

Answer 14

finger-like protrusions rich in actin

(sense where they want to attach, and direction of
movement)

Question 15

what protein overlies these protrusions

Answer 15

Vinuncilin

Question 16

what are Lamellipodia

Answer 16

are sheet-like protrusions rich in actin filaments that attach to the
substratum

Question 17

how do these specialised structures interact to move the cell

Answer 17

first the filopodia are extended to find support to hold onto (focal adhesions)

Lamellipodia then attach to the substratum to provide support during movement

Movement of the cell body occurs, with retraction of the dorsum

Question 18

how is cell movement controlled

Answer 18

within cell to coordinate what is happening in different parts (where to extend and retract)

regulate adhesion/release of cell-ECM receptors

outside control to respond to external influences:
sensors
directionality

Question 19

There are two types of cell motility……

Answer 19

Hapoptatic motility:(movement with no direction)

Chemotactic motility:
(movement in which the cell senses a stimulus and goes towards
it)

Question 20

what does cell movement involve regardless of type

Answer 20

changing cell shape

Question 21

What are the four main stages of cell movement?

Answer 21

Extension
Adhesion
Translocation
De-adhesion

Question 22

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

Answer 22

Focal adhesions

Question 23

what ways can Actin be found as

Answer 23

as small soluble globular monomers (G-actin)

in large polymerized
filamentous polymer (F-actin)

Question 24

Describe the polarity of acting filaments

Answer 24

They have a plus end and a minus end

The monomers preferentially get added on at the plus end

Question 25

how does actin filament polarity change in response to signal

Answer 25

signal (nutrient source) at one end of the cell F-actin at the other end will disassembles the subunits will diffuse to the side with the signal. reassembly of subunits at new site )this facilitates movement).

Question 26

Filament organization and structure allows what structures to be made

Answer 26

Stress fibres (anti-parallel contractile structures) Filopodium (bundle of parallel filaments) Lamellipodium (branched and cross linked filaments)

Question 27

what happens to monomer (G actin in solution)

Answer 27

polymerises very quickly, because the lowest energetic state is as a filament but you can’t just have loads of filaments in the cell. sequestering proteins, store monomers until they are required.

Question 28

the cycle between | G-actin monomers and F-actin is known as....

Answer 28

actin dynamics

Question 29

is the rate limiting step in actin dynamics

Answer 29

Nucleation (nvolves the formation of trimers | to initiate polymerization)

Question 30

What protein complex is important in initiating polymerisation?

Answer 30

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

Question 31

describe the elongation step of actin dynamics

Answer 31

brings monomers (usually sequestered) to the filament.

Question 32

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

Answer 32

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

Question 33

what do capping proteins do

Answer 33

prevent further growth of the filament | Can be used to regulate directionality of growth

Question 34

Name some + end capping proteins.

Answer 34

CapZ Gelsolin Fragmin/severin

Question 35

what is role of severing

Answer 35

used to prevent low rate of growth/shrinking of very long filaments

Question 36

what happens to actin filaments in severed populations

Answer 36

grow and shrink more rapidly

Question 37

Name some severing proteins

Answer 37

Gelsolin ADF Framin/severin Cofilin

Question 38

Name some - end capping proteins.

Answer 38

Tropomodulin | Arp complex

Question 39

Cross-linking and bundling are of two types:

Answer 39

1) actin filaments and alpha-actinin, which forms a contractile bundle (loose packing allows myosin-II entry) 2)The other type is actin filaments and fimbrin, which forms parallel bundling with tight packing

Question 40

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

Answer 40

They can be bundled or cross-linked

Question 41

Name some proteins involved in these processes.

Answer 41

``` Alpha-actinin Fimbrin Filamin Spectrin Villin Vinculin ```

Question 42

Which protein allows branching of the actin filaments?

Answer 42

Arp2/3 binds providing different nucleation site

Question 43

At what angle do they branch?

Answer 43

70 degrees

Question 44

Summarise the actions of Arp2/3.

Answer 44

They initiate nucleation They cap filaments They cause branching

Question 45

Describe what causes the gel-sol transition.

Answer 45

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

Question 46

what Actin activities occur during cell movement

Answer 46

``` includes disassemble, nucleation, branching, severing, capping and bundling ```

Question 47

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

Answer 47

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

Question 48

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

Answer 48

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

Question 49

Signalling mechanisms that regulate the | actin cytoskeleton:

Answer 49

1 - ion flux changes (i.e. intracellular calcium) 2 – Phosphoinositide signalling (phospholipid binding) 3 – Kinases/phosphatases (phosphorylation cytoskeletal proteins) 4 - Signalling cascades via small GTPases