Hallmarks of cancer Flashcards
Hallmarks of cancer
- evading growthsuppressors
- avoiding immune destruction
- enabling replicative immortality
- tumor promoting inflammation
- activating invasion and metastasis
- inducing angiogenesis
- genome instability and mutation
- resisting cell death
- deregulating cellular energetics
- sustaining proliferative signaling
enabling characteristics
tumor promoting inflammation
genome instability and mutation
sustaining proliferative signaling
only 1 allele needs to be mutated
evading growth suppressors
restriction point in cell cycle = very important
phosphorylation of Rb is needed to release R point (checkpoint)
Rb pathway is impaired in 95% of all tumors
can be either loss-of-function or gain-of-funtion
Li Fraumeni syndrom
hereditary mutation in TP 53
avoiding immune destruction
create lack of T-cell recognition by:
- tumor cell no longer expresses certain antigens
- MHC class I becomes deficient
- production of immunosuppressive proteins
- expression of inhibitory cell surface proteins
ex. high PDL1 expression hides tumor from immune system
enabling replicative immunity
senescence = metabolically active but can no longer enter the cell cycle (bc loss of telomeres)
when p53 is absent–> telomeres get stuck together during replication
w/ telomerase: cancer
w/o telomerase: mitotic catastrophe
activating invasion and metastasis
inactivation of E-cadherin
degradation of ECM (by proteolytic enzymes)
epithelial tumors undergo epithelial-mesenchymal transition
inducing angiogenesis
when tumors have no blood vessels, size is limited to 1-2 mm
stimulated by lactate
resisting cell death
ex. p53 mutation, over expression anti-apoptotic factors etc.
deregulating cellular energetics
in proliferative tissue, mostly lactate is produced in stead of ATP, but you get building blocks
Warburg effect (when this happens in tumors)
TSG suppress Warburg effect
lactate stimulates angionenesis
