Cancer Flashcards
Two general characteristics how cancer is defined
Reproduce beyond the restraints of normal cell division
Invade and colonize territories reserved for other cells
What is tumor
Another name neoplasm
Relentlessly growing mass of abnormal cells
How the tumor is called if it is clustered together in a single mass
Benign tumor
Characteristics of malignant tumor
Reproducing and
Have an ability to invade surrounding tissues
If malignant tumor invade and form secondary tumors, it is called
Metastases
How malignant tumors are spread
Usually by blood steam or lymphatic vessels
When a tumor is considered a cancer
Only if malignant
As single mutation is not enough to
Convert a healthy cell into a cancer cell
What give rise to cancerous cells (hint: errors)
Several, independent, rare, unexpected accidents that occur in a cell and during cell division
What is the most widespread cancers among men and women (3 of each)
Males: prostate, lung, colon
Women:Breast, lung, colon
What cancers are rising in numbers
Liver
Why there are picks and then ascending of incidence of some cancer?
Because new technologies were discovered to help to diagnose
Groups of cancer risk factors (5)
- Biological (sex, age, gender, etc.)
- Environmental
- Exposure to known carcinogens
- Bacteria and viruses
- Lifestyle
Three pathways in which cancer cells have alternations
- Glycolysis
- Corresponding effects on TCA cycle
- Pentose phosphate pathway (PPP)
What alternations cancer cells in glycolysis
Cells do not couple glycolysis to TCA cycle even if the cells are under aerobic conditions
The convert pyruvate to lactate through fermentation pathway
Why we have an overall trend of increasing cancer cases
The population age, people live longer
cancer cells do not use TCA, so they do not have it?
No, they have it, just do not use it
Why cancer cells prefer to use glycolysis and fermentation, though it produces 15 times smaller ATP
So it uses glycolysis , because it produces ATP very rapidly in cytoplasm . 10 times faster
Also, some cancer might have a limited access to oxygen -> Anoxic theory
By converting pyruvate into lactate, the negative feedback from the TCA cycle does not occur and glucose metabolism can continue at an accelerated rate
Puryvate->lactate also preserves a pool of NAD+ that can still be used for glycolysis. Drives step 6 of glycoslysis, which then allows for step 7 to synthesize of ATP
Glycolysis continues to make important intermediates that can be used for eventually cell replication, this ensures that cancer cells continues to thrive
What happened to cancer cells where mitochondrial DNA was depleted?
Decreased the tumorigenic potential of the cells invitro and invivo
What happens to pyruvate apart from being converted to lactate
It is converted to citrate, and along with other intermediates these are used to increase the presence of acetyl-CoA
TCA cycle does not function in cancer cells, what is done to acetyl-CoA then
Acetyl-CoA is used for the denovo synthesis of FAs ( usually low production of FAs in normal cells)
Cancer cells need more FAs for
synthesis of more phospholipid bilayer for division
What mutation is usually found in cancer cells
PI3K, kinase is more active
Why PI3K is important
PI3K signalling act as a regulator of glucose uptake by promoting the expression of GLUT1 mRNA and translocation of the protein to the cell surface
Also affects GLUT 4
Downstream signalling of PI3K ( affect)
regulate cellular processes
Cell survival, proliferation, and growth
Ribose 5 phosphate: how it can be used and why it is so important for cancer cells
Structural component of nucleotides
Cancer often has elevated DNA synthesis rates, and therefore require more nucleotides
Increased arability of nucleotides allows for increased bioactivity, proliferation and growth
What changes happen in PPP in cancer cells
Overexpression of transketolase and trans aldolase
what pathway yields more ATP : glycolysis or PPP
Net ATP with PPP: 3 atp
Net ATP form glycolysis : 2
Why PPP is needed for cancer cells apart form energy and ribose-5 -phosphate
Increassed denovo synthesis of FAs because increased levels of Acetyl-CoA
and
Increased rates of the PPP pathways, which increassed NADPH production
Connection of cancer, PPP and glutathione
PPP is essential for tumor cell immortality
Reduced glutathione protects the cell by destroying hydrogen peroxide and hydroxyl free radicals
Regeneration of GSH from its oxidized form GSSH reqiures NADPH-> A decrease in GSH/GSSG ration , leads to an increased susceptibility to oxidative stress (which is implicated in the progression of cancer)
Although, elevated GSH levels increase the antioxidant capacity and the resistance to oxidative stress which has been observed in many cancer cells
As there is an increased glycolysis rate, what mutations cancer cells have
-Glut mutations for increased glucose uptake
Two well-known GLUT 1 inhibitors
Flavonoids (apegenin) by decreasing expressionof the protein
Fasentin (inhibits transporter function)
Cancer cells increase production of FA for the lipid bilayer with what enzymes (3)
ACLY (ATP citrate lyase) ( conversion of citrate to acetyl-CoA)
ACC (acetyl-CoA carboxylase)
FAS ( fatty acyl synthase complex)
How PPP yields more ATP than glycolysis
It skips the step of PFK-1 that uses ATP, from glucose 6-phosphate to ribulose 5 phosphate and then immediately to G3P
