ANSWERS WITH COMPLETE SOLUTIONS
What causes a cancer cell to go rogue?
chemicals, virus, radiation
What are the steps when a cancer goes rogue?
1) normal cell then a genetic change to initiated cell.
2) initiated cell then selective clonal expansion to pre-neoplastic lesion.
3) Pre-neoplastic lesion then genetic change to malignant tumor
4) Malignant tumor then genetic change to clinical cancer
5) clinical cancer then genetic change to cancer metastasis
Hallmark #1
Self-Sufficiency in Growth Signals
Hallmark #1 means
Self-Sufficiency in Growth Signals
Cell growth is normally tightly regulated, requiring a pro-growth signal.
Cancer cells bypass this requirement in a number of ways
How does cell signaling work?
Pro-growth molecule (ligand) binds to extracellular domain
,Intracellular domain becomes active
Signaling cascade proceeds
Pro-growth proteins are transcribed
How do cancer cells become self-sufficient?
Abnormal ligand production, autocrine (self) signaling
Induced paracrine (external) signaling
Upregulated receptor levels
Mutation-induced constitutive signaling
Hallmark #2
Insensitivity to Anti-Growth Signals
Normal cells need to overcome anti-growth signals in order to divide
Anti-growth signals can be both normal and/or induced
Anti-growth signals can originate either internally or externally
Hallmark #3
,Unstable DNA
This is an "enabling" hallmark
Required for tumor progression
Can lead to drug resistance
If DNA became stable, the tumor would survive
Two main forms of DNA instability: Genetic Instability and Chromosomal Instability
Hallmark #4:
Metastasis
The transmission of cancer cells from the original site to one or more sites elsewhere in
the body by the way of blood vessels or lymphatics
Hallmark #5
Evasion of Apoptosis
Apoptosis is a cell SUICIDE mechanism.
Its hallmarks are:
Cell volume loss
, Membrane blebbing and formation of apoptotic bodies, DNA fragmentation and
condensation, Cytoskeleton collapse, Engulfment by immune cells, Non-inflammatory
Hallmark #6
Abnormal Cellular Metabolism
• Most mammalian cells under normoxic conditions pursue oxidative phosphorylation of
glucose.
OXPHOS = 38 molecules of ATP/molecule of glucose.
Cancer cells in contrast metabolize glucose through glycolysis.
Glycolysis = 2 molecules of ATP/ molecule of glucose.
Phenomena of aerobic glycolysis in cancer cells was first observed by Nobel Prize
winner Otto Warburg
• Warburg Effect
Hallmark #7
Angiogenesis
Angiogenesis occurs when there is an imbalance: the angiogenic switch
Hallmark #8
Inflammation
Hallmark #9
Evasion of the Immune System