Wk 24 Flashcards
External control of the cell cycle is by?
What point in the cycle does this occur?
Growth Factors
Throughout G1 only (before restriction point)
Internal control of the cell cycle is?
Where are they? (3)
- What are they checking?
Restriction points
End of G1 to enter into S: Can DNA synth begin?
–> if there has been enough GF and the conditions are right for DNA replication, is DNA intact?
End of G2 to enter into Mitosis: Can cell commit to mitosis?
–> Has DNA been correctly replicated?
Metaphase in Mitosis before anaphase: Spindle checkpoint
–> Are chromosomes attached to spindle and aligned along equator?
What is Anoikis?
Cell detachment mediated apoptosis
What are the 6 hallmarks of cancer cells?
- Evading growth suppressors
- Producing own growth signals
- Angiogenesis
- Metastasis
- Replicative immortality
- Resisting cell death
What is a carcinoma and what percentage of human cancers are carcinomas?
Cancer from epithelial cell origin
90%
What is the most fundamental trait of cancer?
The ability to sustain chronic proliferation
Sustained proliferative signalling linked to gene mutations in which genes?
Proto-oncogenes
What do tumour suppressor genes do?
What do mutations do to these genes?
Encode proteins that limit cell growth and proliferation (halt cell in G1)
Can switch off or inactivate tumour suppressor genes= cancer
How do cancer cells evade programmed cell death?
Anti-apoptotic proteins up-regulated and pro-apoptotic proteins down regulated
How do cancer cells enable replicative immortality?
They turn on the enzyme telomerase so they can replicate forever
How do cancer cells induce angiogenesis?
When does this happen?
Secrete angiogenic factors (e.g. VEGF) that stimulate angiogenesis
When cells in the tumour become too far away from the blood supply and send emergency signals for angiogenesis
What is the process of epithelial-messenchymal transition?
Disruption of normal cell adhesion induces loss of cell polarity (allows cells to acquire a motile and invasive phenotype)
Secretion of what promotes cancer cell migration and invasion and how does it do it?
Secretion of proteases
degrades basement membrane/ ECM compounds
What are the emerging hallmarks of cancer cells?
- Deregulating cellular energetics
- Avoiding immune destruction
What are the enabling characteristics of cancer cells?
- Genome instability and mutation
- Tumor promoting inflammation
What is the major bioenergetic adaptation in cancer? (and what is the technical name?)
Upregulation of aerobic glycolysis (Warburg effect)
How do cancer cells avoid the immune system?
Emerging
Reduce the expression of tumour antigens on their surface
Also express surface proteins that induce immune cell inactivation
What is the ‘stem cell model’ ? (also called hierarchical model)
Only stem cells contribute to tumour growth
What is the 1st phase of carcinogenesis?
immortalization of a normal cell followed by its neoplastic transformation