Cancer Biology - Resisting Cell Death

3 classes of cell death

necrosis, anoikis, apoptosis

necrosis

pathological death caused by external factors, uncontrolled due to mechanical stress

anoikis

“death on detachment”

apoptosis

programmed cell death or caspase mediated

physiological conditions involving apoptosis

cell destruction in embryonic development for pattering, normal destruction of cells accompanied by replacement proliferation, involution of thymus in early age

pathological conditions involving apoptosis

drug induced cell death in tumors, viral induced cell death, degenerative diseases, myocardial infractions & other heart disease, cytoxic T cell induced cell death (immune rejection)

in apoptosis, is BCl2 an oncogene or a tumor suppressor gene?

BCl2 is an oncogene because it serves to suppress apoptosis and BCl2 up-regulation occurs in many cancers. If you increase BCl2, it leads to more cell division

extrinsic

cue to die comes from outside of cell

intrinsic

cue to die comes from inside of cell

caspase proteins

serine proteases that act like scissors

initiator caspases

cuts other caspase proteases such as caspase 8 and 9

executioner caspses

cut a variety of targets such as caspase 3

how is a caspse activated?

when a procaspase is cleaved into a caspase

what are the 10 steps of intrinsic cell death?

P53 senses DNA damage. 2. P53 activates PUMA and NOX. 3. PUMA and NOX inhibit BCl2. 4. BAX and BAK “open” or form channels. 5. Cytochrome C enters cytoplasm. 6. Cytochrome C binds to Apaf-1. 7. Formation of apoptosome. 8. Apoptosome cleaves initiator caspase, pro-caspase 8 or 9. 9. Initiator caspase, caspase 8 or 9 cleave executioner procaspase 3. 10. Executioner procaspase 3 cleaves caspase 3 in cell and cell death occurs.

what are the 6 steps of extrinsic cell death?

1. cell to cell interaction. 2. death receptor activated. 3. death receptor recruits and activates FADD. 4. FADD activates TRADD. 5. TRADD recruits and cuts procaspase 8. 6. Caspase 8 cleaves procaspase 3 and inhibits BCl2 to amplify the signal and cell death.