lecture 1 - nature and hallmarks of cancer Flashcards
What are the 6 hallmarks of cancer?
- Self-sufficient in growth signals
- Insensitivity to anti-growth signals
- Evading apoptosis
- Limitless replicative potential
- Sustained angiogenesis
- Tissue invasion and metastasis
What did Edmond H. Fischer & Edwin G. Krebs discover? Which hallmark of cancer does this link to?
Reversible protein phosphorylation as a regulatory mechanism. Hallmark 1: self- sufficient growth signals
What did Leland H. Hartwell, Tim Hunt and Sir Paul M. Nurse discover? Which hallmark
Discovered the key regulators of the cell cycle.
Hallmark 2: insensitivity to anti-growth signals
What did Sydney Brenner, H. Robert Horvitz and John E. Sulston discover? Which hallmark
Discovered the genetic regulation of organ development and programmed cell death. Hallmark 3: evading apoptosis
What did E.H. Blackburn, Carol W. Geider and Jack W. Szostak discover? Which hallmark
Discovered how chromosomes are protected by telomeres and telomerase. Hallmark 4: limitless replicative potential.
What did William G. Kaelin, Sir Peter J. Ratcliffe and Gregg L. Semenza discover? Which hallmark
Discovered how cells sense and adapt to oxygen availability. Hallmark 5: sustained angiogenesis
Judah Folkman
Raised the concept of anti-angiogenesis therapy
HIF1-a
Cellular sensor of oxygen
In normoxia: it undergoes prolyl hydroxylation then proteasomal degradation
In hypoxia: it leads to greater transcription at the hypoxia response element
E-cad
tumor suppressor protein
N-cad
enhances cell motility which promotes invasion of epithelial cells
Integrins
promotes adhesion between cancer cells
MMPs
MMPs (matrix metalloproteinases) degrade the ECM (extracellular matrix) and facilitates cell migration
LOX
LOX (lysyl oxidase) key enzyme in tumor progression, forms blood vessels
Describe what is EMT and its steps.
EMT (epithelial to mesenchymal transition): allows a polarized epithelial cell to assume a mesenchymal cell phenotype
- the primary tumor cell undergoes EMT (E-cad decreases while N-cad and integrins increases)
- tumor cells invade through basement membrane (increase MMPs and LOX)
- tumor cell develops pseudopodial protrusion and undergoes intravasation (metastasis) where they migrate away from the epithelial layer it originated from
emerging hallmarks of cancer
“emerging”
7. reprogrammed energetic metabolism
8. avoiding immune destruction
“enabling”
9. genome instability and mutation
10. tumor-promoting inflammation
Warburg effect
did it lead to any hallmark?
most cancer use aerobic glycolysis and lactic acid fermentation for energy generation
James P. Allison, Tasuku Honjo
hallmark and explain?
discovered the body’s immune system can be harnessed to attack cancer cells. Hallmark 8: avoiding immune destruction; detection of cell surface markers on cancer cells prevents destruction by T-cells
what is the multi-hits model?
cancer development model - one mutation is not enough to lead to cancer
what makes genome instability and mutation an “enabling” hallmark of cancer?
cancer cells have much higher mutation rates. it is a dynamic disease and follows a multi-hits model.
what makes tumor-promoting inflammation an “enabling” hallmark of cancer?
- all tumors infiltrate immune cells
- acquisition of capabilities
- produce more reactive oxygen species, further causing genome instability
