L8 - Cell cycle Flashcards
Undifferentiated state: what makes this state ideal for cancer cells?
Proliferation: Undifferentiated cells have a high capacity for self-renewal and can divide rapidly.
Resistance to apoptosis: in an undifferentiated state are often resistant to apoptosis
Invasion and metastasis: Undifferentiated cancer cells have the ability to invade surrounding tissues and migrate to other parts of the body. This is because they have retained some of the properties of embryonic cells, which can migrate during development.
Increased plasticity: Undifferentiated cancer cells are more adaptable than their differentiated counterparts, meaning that they can respond to changes in their environment more easily.
Decreased immune surveillance: Cancer cells in an undifferentiated state often have reduced expression of surface markers that would normally make them recognizable to the immune system as abnormal or foreign.
Metabolic plasticity: Undifferentiated cancer cells have an altered metabolism that allows them to adapt to different nutrient and oxygen conditions.
Types of signalling that influences cell cycle?
- Differentiation factors
- Growth factors
- Motility factors
- Survival factors
- Nutrients (mTOR)
General cell cycle process
G0 - quiescent state
G1 - growth, R phase located here, determines if there are enough metabolites and signals to continue the cycle
S - genome replication, largest metabolic demand
G2 - organelle synthesis, not sustainable to maintain two sets of chromsomes, readily continues when possible
M - PMAT
R point: what is it and what does it do?
Restriction point of the cell cycle
Up until this point, cells are responsive to mitogenic growth factors and can have its growth inhibited and promoted but after this the cell cycle moves unidirectional and cannot be inhibited (unless the cell gets destroyed - ie p53)
Cyclins: what CDKs do they pair with and in what parts of the cell cycle do they get activated?
Cyclin D - CDK4/6, first Cyclin/CDK complex activated, promotes the movement through R phase
Cyclin E - CDK2, after C/CDK4/6, promotes movement from G1 to S
Cyclin A - CDK2, ????
Cyclin A - CDC2, movement through S phase to late G2
Cyclin B - CDC2, movement through M phase
Do cyclins or CDKs determine movement through the cell cycle?
CDKs are continually expressed through the cell cycle, cyclin expression and proteolysis determines cell cycle movement
Cyclin D: What signals influence its production and what is its activation like?
Mitogenic signalling from multiple sources feed in to the transcriptional control of cyclin D1
Gets synthesised, phosphorylated and translocated to the nucleus, binds with CDK4/6 and phosphorylates Rb which then detaches from E2F, allowing for genes that promote the cell cycle to be activated (includes cyclin E production)
RAS, one mitogenic growth factor, results in cyclin D transcription, as well as mTOR production
mTOR: what is it and what does it do?
??
Cell nutrient sensor
How does Rb present during the cell cycle?
During early-mid G1 it is either dephosphorylated or hypophosphorylated and bound to E2F, blocking transcription but from G1 until the rest of the cell cycle it is hyperphosphorylated
CDKI: what are they, what do they do, what are they (in)activated by, and what examples are there?
Cyclin dependent kinase inhibitors
Bind to CDKs and prevent their action? Or prevent cyclin binding ?? look this up
Induced by growth suppressors - TGF-beta,p53
Antagonised by oncogenes - myc, Akt
p21 (prodcued by p53), p27, p57 these all inhibit Cyclin E/A/A/B, and p16/15/18/19 (inhibit cyclin D)
How frequent are cell cycle gene mutations in cancer?
Very, many are present in around 80%
