Lecture 1 Flashcards
What are the 8 (previously 6) commonly acquired traits of cancer causing cells?
1) Self-sufficiency in growth signals
2) Insensitivity to growth-inhibitory signals
3) Tissue invasion and metastasis capability
4) Limitless replicative potential
5) Sustained angiogenesis
6) Evasion of programmed cell death
7) Reprogramming of energy metabolism
8) Evading immune system
Name two enabling events
Loss of genome surveillance and checkpoint control Destabilisation of nuclear organisation
Why are there so many ways to acquire the same trait?
Mutation of several pathways leads to same consequence for the cell In each pathway mutation of several different genes or proteins can have same effect
What three measures are used in classifying cancers? Why is this not the best way?
Site of origin
Cell type
Age of onset
Does not look at molecular level
Why do stem cells require fewer mutations on average to become a cancer cell?
Already have unlimited proliferative ability
Why are most tumours described as heterogeneous?
Made up of both neoplastic and pre-neoplastic cell populations
How can two independent cancers come from the same origin?
Same starting mutation but different mutation later on lead to them being separated by healthy tissue which has not developed the caner causing mutation
What do normal cells require to move from quiescence to profilerence?
Mitotic signal; paracrine or endocrine
What are the steps from a mutation to fully invasive cancer
1) Cell acquires genetic mutation - which promotes or allows proliferation 2) Hyperplasia 3) Dysplasia 4) In situ cancer 5) Invasive Cancer - with its own blood supply
How are external signals transmitted into the cell?
Transmembrane Receptors- which then dimerize and phosphoryalte each others tyrosine domains and start an signal transuction pathway
What types of singalling molecules are involved in mitotic signalling?
1) Diffusbale growth factors
2) Extracellular matrix components
3) Cell-to-cell ahgesion/interaction moleclues
How can oncognenes hijack these signal pathways?
Mimicking normal growth signaling
Code forconstitutively active (ligand independent receptors)
Disrupt signal transduction
What are oncogenes?
Gain of function mutations in genes that promote cell proliferation
Dominant mutations
What are tumour supressor genes?
Loss of function mutations in a genes that restrain cell proliferation or guard the genome
Recessive mutations (often underlie familial cancers)
Outline 2 examples of how cancer cells can de-regulate and acquire self-suffiency in growth signals
Example 1: the ErbB2/Her2/Neu
Overexpression of receptor = hypersensitivity to ligand. Acitvates intracellular kinase which has complex set of effects on both apoptosis and proliferation
Example 2: RAS
An intra-cellular switch protein which can be permanently on due to mutation. When GDP is bound the protein is inactive whereas GTP bound RAS is active. The swtiching between the two have effects on the shape of the entire protein, with active RAS being able to bind down-stream proteins in cell signalling pathways. in non-cancer cells RAS will hydrolyse GTP to switch off; this is dependent on RAS-GAP, inserting an argiunine side chain directly into the active site, which work with threonine and glutamine, of the RAS itself, to promote GTP hydrolysis.
What is herceptin?
Monocolonal antibody that blocks Her2 receptor and extends life in breast cancer patients
Howvere, the life extension is only for months and the quality of life is severed inpacted
What percentage of all cancers have RAS mutations?
25%
What are viral oncogenes?
Some viruses have acquired proto-oncogenes which they will pass onto host cells; conferring a growth advantage to the cell, helping to propagate the virus but causing cancer in the host.
