Cancer traits I (FS - Week 7) Flashcards
Name the stages of a normal cell cycle
G0 - resting state (quiescent)
G1 - cell growth - increases in size and contents are duplicated
S - DNA replication
G2 - preparation for mitosis - cell grows and proteins develop
M - mitosis and cytokinesis
What is mitosis
DNA condense into chromosomes and are pulled apart by mitotic spindle
Name the phases of mitosis
Prophase
Prometaphase
Metaphase
Anaphase
Telophase + cytokinesis
What is the role of cyclins and cyclin dependent kinases
Cyclins drive the events of the cell cycle by partnering with the cyclin-dependent kinases (Cdks).
A lone Cdk is inactive, but the binding of a cyclin activates it, making it a functional enzyme and allowing it to modify target proteins.
What happens in an abnormal cell cycle
unreplicated, mutated, damaged DNA block the cell cycle checkpoints - the cell cycle then progresses unchecked leading to further mutations and cancer
How do cancer cells maintain proliferative signalling
- they synthesise GFs and GF ligands which creates a positive feedback signalling loop
- They stimulate normal cells with tumour associated stroma to produce GFs
- upregulate receptor expression leading to sensitisation to ligands
- activate downstream signalling pathways of these receptors
How do cancer cells evade growth suppressors
They use antigrowth signals to force cells to quiescent (G0) state or induce cells into postmitotic states
cancer cells avoid antiproliferative signals that normal cells respond to
What is angiogenesis and what is it used for? In normal cells when is angiogenesis important?
Angiogenesis is the formation of new blood vessels/capillaries from pre-existing blood vessels
It is essential for the survival of normal tissue to supply nutrients and oxygen, removing waste products and CO2
It is important during embryonic development, wound healing and reproductive cycle
Why do tumours need angiogenesis and what is the main factor cancer uses to achieve this?
Tumours require new blood vessels to obtain nutrients and oxygen and evacuate carbon dioxide and metabolic waste same as normal tissues.
Tumour hypoxia leads to upregulation of angiogenesis factors like vascular endothelial growth factor (VEGF). that stimulate directional endothelial cell growth
What is the angiogenic switch
It is the counterbalancing positive and negative signals that encourage or block angiogenesis
Describe the steps in tumour angiogenesis
a. Tumours cannot grow beyond 2 mm3 due to limited delivery of O2 and nutrients, so cells become hypoxic.
b. Hypoxia inducible factors increase expression of angiogenic factors.
c. New network of blood vessels grows in and around the tumour (more oxygen and nutrients), tumour grows (new route for cells to shed off and metastasize).
What is apoptosis and necrosis
Apoptosis is a form of programmed cell death used in physiological scenarios to remove unwanted or damaged cells
Necrosis is a form of unregulated cell death or cell injury due to premature death of cells in living tissue by autolysis (self-digestion). Necrosis is caused by external factors, such as infection or trauma.
How do cancer cells resist cell death in terms of apoptosis
- Apoptosis - p53 encourages apoptosis by upregulating Bax (proapoptotic) in response to DNA damage which causes the release of cytochrome C which activates caspases
- Tumour cells have loss of p53 function and increase antiapoptotic regulations they downregulate proapoptotic signals
What are the morphological changes during apoptosis
Apoptosis: cytoplasmic shrinkage, chromatin condensation, nuclear fragmentation, plasma membrane blebbing leading to formation of apoptotic bodies. These will be taken up by phagocytes and degraded within lysosomes.
What are the morphological changes during autophagy?
Autophagy: cellular organelles, such as ribosomes and mitochondria, are enveloped by intracellular vesicles (autophagosomes) which fuse with lysosomes where degradation occurs.
