Cancer 9: external factors controlling division Flashcards

1
Q

WHat is cell behaviour?

A

Term used to describe the way cell interact with external environement and their local environement-particulalry proliferation and motility

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2
Q

What are the 2 form of external influences that cells can detect?

A

Chemical-hormones, GF, ions, ecm, molecules, nutrients-
Physical-mechanical stress, temperature, topography of ECM

in cancer the main one are GF, cell cell adhesion and cell-memrbane adhesion

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3
Q

How do cells adhere in culture?

A

Spreads out using lamellipods-polarised as a motile cell
spreading isinitial contact

definitly not a gravity dependent event-cytoskeleton related
If a cell sticks ontop of another one-doesnt spread
as spread more likely to replicate on culure
in agar-low S rate chance
(with presence of GF)
=> ECM is required for division

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4
Q

What is the relation between ECM and cell proliferatio?

A

Suspension-not make protein or DNA
require ECM and spreading to being the proper process
ECM is required for survival-can undergo apoptosis if bad ECM

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5
Q

WHat is the relation between ECM and cell differentiation?

A

cell phenotype can be determined by composition of the matrix
just collagen-form loose ball of cells (even epithilial cells)
With a basal lamina-form a lumen and organise themselves in oragnoids (and produce the right proteins)-mammary glands produce milk)

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6
Q

How do cells attatch and signall through the ECM? What is the main exemple?

A

Cell have receptors on their surface to bind ECM
Have cytoplasmic domain and extracellular (connect to cytoskeleton-link bewteen ECM and cell interior

Most well understood-Intergins
heterodimer of a and B chain-associate in head region-where binds ECM-to short AA sequence-like-arg-gly-asp (RGD)
Short cytosolic region
About 20 combinations of integrins
Bind the AA sequence find in some matrix moelcule-some can bind many, some only one

Focal adhesions are clusters of integrins
Hemidesmosomes are also clusters
ICAM and VCAM also bind integrins

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7
Q

How does the ECM signall the cell? Describe how?

A

ECM receprtors like intergins transfer the signal
Integrins can be flexed or extended (head down or up)

When binds to matrix-transduce a signal through to the cell=with recruited proteins (like focal adhesion kinase)
ECM/integrins direct what the signal-
amount of roce generated b focal adhesion can activate specific proteins

Internal signals also activate integrins to make them “sticky”-head up-and only after that signal can it bind ECM and recruit signalling proteisn
depending on the cell it can be constantly high affinity

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8
Q

Why do cell in culture formin a monolayer stop proliferating?

A

Either cell to cell contact tell them to stop-no more space–cell to cell inhbition
But also idea that its because of the competition for GF-not enough for everyone to divide-density dependence of cell division

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9
Q

How do GF and ECM combine to lead to proliferation?

A

No need for detail
But TKR-through MEKKK pathway-signal nucleus
Integrins can also activate the same pathway
But inidivudally its weak
need booth for strong and stable activation

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10
Q

What are the 2 outcomes of cells contact?

A

short term-transient interactions bewteem cells which do not become stable cell-cell junction
Long term-stable interaction-uses cell-cell junctions

Most non epithelilial cells collide they dont form junctions and actually try and move around from one another-contact inhbition of locomotion
epithelial cells are specialised in cell junction-dont repel

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11
Q

What are the types of epithelial cell-cell jucntion

A

Either as belts or discrete spots
Tight junctions
GAp junctions
Desmosomes-adhesion belt+fical contact-adherens junction

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12
Q

What happens when epithalial cells touch in culture? What happens when you remove Ca?

A

They spread along the junction point and actually take more space than sum of each cell-
When remove Ca-cant form junction-cell near but not joined-high proliferation
re-add Ca-stop proliferation

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13
Q

What are adherens?And cadherins? What is a main player

A

On each cell-bind each other- (on different cells)-Cadherins is the ca dependent form
intra cellular: Cadherin bind Bcatenin-binds acatenin which binds actin filament
B-catenin degradation mutation leads to multiple polyp in colon

when cells bind- a and B catenin is inside
If adherens of the cells around bound to another cell/junctions breakdown-cytoplastic b-catenin is very quickly degraded by APC complex
When not degraded-> B catenin is pro-proliferative. Degradation is how cell-cell contact inhbits proliferation
But in some cancer, APC complex inactive-becomes part of TF complex (LEF1)-leads to prolifeation

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14
Q

What adhesion associated signalling pawthways are associated with proliferation

A

Adherins and B-catenin
Cultersing of cadherins after contact can activate GTPases (RAC uo, Rho down)
Some GF receptors are associated with cell to cell junction-reduce capactity to promoter proliferation

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15
Q

WHat happens when cell lose ability to talk to each other?

A

proliferate uncontrollably-no density dependence
Less ahderent and mutlilayer-lose contact inhbition of locomotion and acnhorage dependent
Epithelia breakdown cell-cell
not hayflick limited-> cancer

this is a lot of cacer

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16
Q

What is the consequences of loss of contract inhbition of locomotion in cancer/

A

Promotes formation of solid tumours

but also allows invasion because allows digging through other tissue-

17
Q

What parts of signal transduction pawthways can be protooncogenes?

A

Receptors, signalling intermeditated and signalling tarfets are protooncogenes by default
if turned on too much-become oncogene
short circruit leading to uncontrolled proliferation

18
Q

What is an oncogene? protooncogene? eg?

A

Mutant gene which promotes uncontrolled mutation
proto-the still normal version

exemple: ras, EGFR

if a pathway requires other inputs-if one in activated as oncogene, then as soon as by chance the other activate-then it goes
But more mutations also cause more pawthways to activate and regulation to dissapear

19
Q

What is the most dangerous part of cancer/

A

its not the growth but the invasion
and most adult cancers are epithelial–

to metastase-cell-cell adhesion must be downregulated
cell must be motile
Degradation of ECM to invade
degree of clell cell adhersion is inidcation of how differentiated it is