Lecture 4 Flashcards
How do cancer cells sustain proliferative signaling?
Mutated proto-oncogenes (oncogenes) yield a gain of function and overstimulate cell division.
The 10 hallmarks of cancer include
Sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, deregulating cellular energetics, avoiding immune destruction, genome instability and mutations, and tumor promoting inflammation.
How do cancer cells ignore growth suppressors?
Both alleles of a tumor suppressor may be mutated.
How do cancer cells resist cell death?
Loss of intracellular proteins that monitor DNA damage, such as P53. Pro survival genes (Bcl-2 family if proteins) may be over expressed as well.
How do cancer cells enable replicative immortality?
Disregard Hayflick limit through loss of contact inhibition, inactivate pRb and/or P53 (tumor suppressor genes), express telomerase.
How do cancer cells induce angiogenesis?
Release pro-signaling molecules like vascular endothelial growth factor (VEGF) and/or fibroblast growth factor (FGF).
How do cancer cells activate invasion and metastasis?
Stop expressing anchorage dependence.
How do cancer cells deregulate cellular energetics?
Shut down mitochondria and uptake glucose at a much higher rate.
What is the Warburg Effect?
Cancer cells produce energy primarily via glycolysis, even in aerobic environments.
What are the two populations of cells in a tumor, and where are their relative locations and metabolisms?
Hypoxic glycolytic cells, found far from the blood vessels and produce energy largely via glycolysis, secreting lactate; and oxygenated OxPhos cells, which import lactate to use in oxidative phosphorylation and are located near the blood vessels.
How do cancer cells avoid immune detection?
Primarily develop when immune system is weakened (compromised) or overmatched.
What genomic instabilities do cancer cells have?
Mutations in repair genes, which in turn lead to an increase and accumulation of mutations in the rest of the genome.
What are the breast cancer susceptibility genes?
BRCA-1 and BRCA-2.
Why do tumors activate/promote inflammation?
Associated increase in vasopermiability leads to sustained angiogenesis. Tumor associated macrophages may also promote tumor progression in the microenvironment.
