tumor heterogeneity
can explain the difficulty of predicting patient outcome at diagnosis, of coming up with
effective treatment options, and possibly overcoming drug resistance.
Organic molecules are metabolized by cells
converted from one form into another
Brainpower
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cells can alter their metabolism to fit...
existing conditions
Proteins as metabolic regulators
-metabolism is fast
-enzymes (proteins) catalyze chemical reactions by binding substrates (ligand) and convert
them into products
metabolism of cancer
-aerobic glycolysis
-cancer cells increase uptake of glucose and speed up the rate of glycolysis in order to
siphon off intermediates for anabolic pathways without sacrificing ATP production
Protein Domains - Structure
-domains confer a specific activity (PX domain enables lipid-binding)
- some proteins have more than one domain and multiple activities (ex, Tks5)
,differential gene expression
The expression of different sets of genes by cells with the same genome.
- implies the process is highly regulated
signal transduction
molecular mechanism by which cells receive incoming stimuli, convert and amplify the signal
internally through second messengers, alter effector proteins, and ultimately change cell
behavior
cell receptors
receive incoming stimuli, second messengers that convey and amplify the signal and
effectors that alter cell behavior
cell cycle
control system that undergoes cyclical activation and inactivation of signaling molecules.
major signaling molecules
cyclins and cyclin-dependent protein kinases (Cdks).
- Cyclins bind to and activate Cdks.
- Cdks then phosphorylate
and activate other molecules whose functions enable replication, mitosis, and cytokinesis.
signal transduction pathway controlling the cell cycle passes through the protein pRb.
- Cell cycle progression is initiated by positive growth signals from the cellular environment
called mitogens.
- Active cyclin/Cdk complexes phosphorylate pRb, which in turn releases transcriptional
activators that turn on the expression of genes necessary for cell proliferation.
Another signal transduction pathway enables response to DNA damage
- cell cycle is paused by the protein p53.
- p53 phosphorylation activates its transcriptional regulatory activity, promoting the
expression of the cyclin/Cdk inhibitory protein p21, and therefore cell cycle arrest.
pRB
Tumor suppressor gene that keeps the cell cycle in check until conditons are favourable for
growth.
- mutations in this are common in cancer
, p53
tumor suppressor gene that keeps the cell cycle in check until the genome can be cleared of
damage.
- mutations are common in cancer
Mutations are rare because...
- DNA polymerase has a proofreading function that corrects any mistakes it might introduce
during DNA synthesis. The editing portion of the DNA polymerase is a nuclease that cleaves
the mistakenly added nucleotide so that the correct one can be put in its place. The high
fidelity of DNA polymerase means it is virtually mistake- proof (1/107 nucleotides).
- DNA polymerase is a 1 in a 10,000,000 kind of enzyme
Apoptosis
programmed cell death
- Natural countermeasures that deplete cell numbers
is called programmed cell death
- Pro- and anti-apoptotic proteins of the Bcl2 family hang in the balance in living cells.
- This balance is disrupted when there are superfluous, mislocated, or damaged cells
around.
cell motility
- response for cells to move
- an actin microfilament driven process of reaching out, grabbing on, and squiggling forward
epithelial tissue
- contain differentiated epithelial cells with finite lifetimes.
- Every three days, the intestinal epithelium turns over. Old cells apoptose. New cells take
their place.
stem cells
replacement cells' come from dividing stem cells that are responsible for tissue renewal
- Adult stem cells are developmentally restricted.
-
Tissue renewal - cancer
- cost of tissue renewal is the potential that renewal will occur even in the presence of
normal constraints.
- Such uncontrolled renewal (proliferation) that belies tissue boundaries
(motility/invasion/metastasis; malignancy) is by definition cancer.
4 types of tissue