Unit 1 Flashcards
(76 cards)
Does one mutation always cause cancer?
no, could casue cancer or could just kill cell
What must cancer have?
- a mutation
- sustain proliferative signaling/ sustained angiogenesis
- tissue invasion and metastisis
- evasion of apoptosis
- promoting gene instability leading to mutation
- limitless replicative potential throuhg increased telomerase activity
- self-sufficiency of growth signals
- insensitivity to anti-growth signals
- avoidance of immune system to evade apoptosis
- tumor promoting inflamation
What is angiogenesis?
- production of new blood vessels into tumor for a nutrients
How do cells sustain proliferative signaling?
- cancer cells activate TF to produce angiogenesis
- stimulators such as VEGF or decrease production of growth inhibitors like throbospondin
How does tissue invasion and metastasis happen?
- decrease of cell to cell adhesion through mutant cadherins
- increased cell motility
- ## increase of protease production degrading ECM
What are cadherins?
- protein binding in ECM
What is the seed soil hupothesis?
- metastisis is product of favorable interactions between tumor cells (seed) and organ microenvironment (soil)
What is metastasis?
- colonization of secondary organs
What is a pro of metastasis?
- new resources, more space, possibility for evolution and new mutation
What is a metastasis cons?
- new environment (unknown) more chance of detection, could lose all exploring cells
What is the ras-mapk pathway?
- growth factor bound to receptor
- clustering and autophosphorylation of receptor
- activation of ras
- activation of protein kinases (RAS, MEK, MAPK)
- synthesis of cyclin and CDK activating cell cycle
- then is potentially oncogenic
What is the Jak-Stat pathway?
- binding of ligand to receptor causes receptors to cluster together and phosphorylation Jak molecules
- jack p phosphorylates receptor
- stat molecules interact with R-P and become phosphorylated
- stat-p joins to form dimers
- stat-dimers enter nucleus and bind to DNA of specific genes
- transcription of genes activated
- protein production to stimulate cell proliferation
How do cells avoid apoptosis?
- typically due to p53 mutation
- p53 is typically in every cell but both p53 copies must be mutated
- could be rare or you could inherit mutated p53
- dna is made unstable by dna polymerase mutations, environmental toxins
What is p53?
- genome gaurdian, protein/ tumor supressor gene that is alerted to potential mutations and then tells DNA polymerase to fix or tells cell to kill itself
In a healthy cell what does p53 do?
- p53 binding always stop cells when properly phosphorylated
How do cells obtain limitless replicative potential through increased telomerase activity?
- telomere length is maintained
- 90% of cancer cells have increased telomerase activity
What do telomeres do?
- encode for specific proteins but do protect the genes tahat do
What happens to telomeres as we age?
- decrease telomerase activity
What is the relationship between replicative abilty and telomerase activity?
directly proportional
How do cell have self-sufficiency of growth signals?
- doesn’t rewuire growth signals to continue cell division, makes their own growth signals
- they don’t need something else to tell them when to grow, they just do
- ex. mutant ras protein leading to uncontrolled ras=map K pathway
How do cells maintain insensitivity to anti-growth signals?
- typically during g1 and related to cyclins
- helps evade cell checkpoints
- most true antigrowth signals are g1
How to cells avoid immune system detection and evade apoptosis?
- can camouflage with host cells proteins and receptors to look normal
- could spread to bone marrow to prevent production to finding agents
What does tumor promoting inflammation do?
- cancer cells take over normal inflammatory response of immune cells are subverted to tumor-promoting cells
- now immune system is helping tumor
- cells now secrete pro-survival, pro-migration, and anti-detection factors
- decrease cancer adherance to host cells so they can migrate and colonize.
What does cancer cells de-regulating cellular genetics do?
- often affects metabolism
- increased metabolic rate could be good and bad because available resources will be used faster