Neoplasia (7) - Cancer Hallmarks 3-10 Flashcards
Warburg effect favors what energy usage?
Aerobic Glycolysis
increased glucose -> Lactose
What is the result of the Warburg effect?
Cell creates more metabolites needed for synthesis of cellular components
= cell replication with the cancer cell components!
If tumor cells use Autophagy, what does that allow them to do?
“hibernate” and SURVIVE harsh nutrient periods
- Recycling their own contents
2 mechanisms for evasion of cell death?
DECREASE P53
INCREASE BCL-2 = ANTI-apoptosis
If a cell increases BCL-2, what does that result in?
ANTI-apoptosis = Cell survival
Normally, what shortens on chromosomes over time as the cell divides multiple times?
Telomeres
Once the telomeres are too short, what stops?
Cell division
Once the telomeres are too short for cell division, what results?
Senescence (permanent cell cycle arrest)
What do cancer cells use to stop telomere shortening so they can divide indefintitely?
Telomerase!
Job of Telomerase?
Protects the telomeres from shortening so cell division can occur forever
Tumors cannot enlarge past 1-2 mm without inducing?
Angiogenesis
Normally, there is equal balance between angiogenic inhibitors and activators. What gets turned on for there to be more angiogenic activators?
Angiogenic Switch
What is an important angiogenic activator?
VEGF
What activates VEGF and thus angiogenesis?
Hypoxia and HIF1
RAS and MYC
What are the 3 barriers for cancer cells to get through to metastasize?
- Cell basement membrane
- Into the blood vessel
- Out of the blood vessel
What normally adheres the cancer cells together?
E-cadherin
What reduces E-caderin expression?
Epithelial - Mesenchymal Transition
What does the Epithelial - Mesenchymal Transition do?
Reduces expression of E-cadherin and thus the cancer cells are not held together!
If the cancer cells are not adhered to each other, what has been lost?
E-cadherin
What do cancer cells secrete to degrade the cell basement membrane so they can get into the blood stream?
Matrix Metalloproteases (MMPs)
What immune cells normally defend against and kill tumor cells?
CD8+ Cytotoxic T Lymphocytes
What things can tumor cells express on their surface that CD8+ CTL T cells will recognize?
Self antigen
Oncogenic virus
Tumor cells can decrease expression of what 2 things to evade CD8+ T cells?
- Self antigen loss
2. Class 1 MHC deficient
If a tumor cell is recognized by a CD8+ T cell, what ligand will the tumor cell express?
PD-1 ligand
A tumor cell’s PD-1 ligand will bind?
PD-1 on the CD8+ T cell
What does the interaction between the PD-1 ligand and receptor cause?
INHIBITS THE T CELL
Treatment using Immune Checkpoint Inhibition uses what mechanism for the T cell to kill the tumor cell?
Antibodies against the PD-1 ligand and receptor so the T cell can kill the tumor cell
Failure of DNA mismatch repair will cause what type of mutations in the DNA to accumulate?
Microsatellite (tandem repeats)
What syndrome is germline loss of function of DNA mismatch repair?
Lynch syndrome
Defects in Homologous Recombination Repair factors causes the cell to be unable to fix what?
Double stranded DNA breaks
What are examples of genes that cause defects in Homologous Recombination Repair factors?
BRCA1 and BRCA2
Burkitt’s Lymphoma has what translocation?
MYC-IgH
Acute Promyelocytic Leukemia has what translocation?
RARalpha - PMC
Burkitt’s Lymphoma translocation causes?
Increased transcription!
MYC-IgH
Normally, RARalpha binds?
RA
Normally, RARalpha binds RA and causes?
Neutrophilic differentiation
With Acute Promyelocytic Leukemia, what translocation has occurred?
RARalpha - PMC
RARalpha - PMC translocation will NOT bind?
RA
If RARalpha - PMC translocation occurred and RA cannot bind, what will result?
BLOCKED neutrophil differentiation
= Accumulation of leukemic blasts
Accumulation of leukemic blasts is seen with what disease?
Acute Promyelocytic Leukemia
Decreased MicroRNA’s =
Increased oncogenic RNA
