Cancer traits

Question 1

What are cyclins?

Answer 1

Regulatory proteins that control the progression of the cell cycle.

Question 2

What are kinases?

Answer 2

Enzymes that transfer a phosphate group using ATP to a substrate

Question 3

What is angiogenesis?

Answer 3

The formation of new vessels/capillaries from pre-existing blood vessels (by sprouting)

Question 4

What is angiogenesis important for?

Answer 4

Embryonic development
Wound healing
Female reproductive cycle

Question 5

Angiogenic factors

Answer 5

Stimulate the directional growth of endothelial cells:
VEGF
MMP-2

Question 6

Give examples of endogenous angiogenic inhibitors

Answer 6

Thrombospondin-1
Endostatin
Angiostatin

Question 7

Regulated cell death mechanisms

Answer 7

Autophagy-dependent cell death

Extrinsic apoptosis
Intrinsic apoptosis

Question 8

What does autophagy mediate?

Answer 8

Mediates tumour cell survival and death

Question 9

List some examples of hallmarks of cancer

Answer 9

Sustaining proliferative signalling 
Evading growth suppressors 
Tissue invasion & metastasis 
Limitless replicative potential 
Sustained/inducing angiogenesis 
Avoiding apoptosis 
Avoiding immune destruction

Question 10

What are the normal phases of a cell cycle?

Answer 10

G1 growth phase: cells increase in size, cellular content is duplicated
S phase: DNA replication.
G2 phase: Cell growth in preparation for cell division
M phase: cell divides
(mitosis and cytokinesis)
G0 phase: Resting state

Question 11

Sustaining proliferative signalling

Answer 11

Damaged genes produce (faulty) receptors that activate itself without the presence of a growth signals (i.e. GFs)
Hence activating intracellular cascade (for cell division)
The replicated cells have mutated receptors = uncontrolled growth

Cancer cells can synthesis their own GF & GF ligands = autocrine proliferative stimulation = upregulate receptor expression on cell surface = increased sensitivity to ligands & activate downstream signalling pathways

Question 12

Evading growth suppressors

Answer 12

Cancer cells can block proliferation by:

• Being forced into G0 state (later re-emerging when extracellular signals allow)
• By being induced into post-mitotic states

Question 13

Inducing angiogenesis

Answer 13

Cancer cells stimulate angiogenesis in and around the tumour cells = tumour growth and metastasis

Tumour hypoxia leads to the up-regulation of angiogenic factors i.e. VEGF

Question 14

How does angiogenesis contribute to disease

2 main methods

Answer 14

Insufficient vessel growth: Stroke, myocardial infarction

Excessive vessel growth: Cancer, inflammatory disorders

Question 15

What is regulated cell death and list examples

Answer 15

RCD results from the activation of one or more signal transduction modules (Either pharmacologically or genetically modulated)
Examples:

Autophagy-dependent cell death
Extrinsic apoptosis
Intrinsic apoptosis

Question 16

Avoiding apoptosis

Answer 16

Cancel cells can ignore signals I.e. P53 tumour supressor signals
(It activates apoptosis of cells with damaged DNA

Question 17

Tissue invasion & metastasis

its cascade

Answer 17

Cancer cells can escape the primary tumour mass and colonise new areas of the body through the circulation
This invasion is enabled by EMT (Epithelial-mesenchymal transition)

Invasion of basement membrane 
Intravasation of cancer cells into nearby blood and lymphatic vessels
Survival of cancer cells in circulation 
Extravasation 
Micrometastases 
Colonization

Question 18

Limitless replicative potential

Answer 18

Normal cells have a replicative limit (Hayflick limit 40-60 times)
Every time a cell is replicated it loses a bit of DNA
When telomeres are lost the coding sequence starts to disappear = production of faulty genes

Cancer cells don’t activate apoptosis
Instead activate enzyme telomerase = adds DNA bases to telomeres = keep dividing

Question 19

Deregulating cellular energetics

Answer 19

Cancer cells can reprogram glucose metabolism (energy metabolism to glycolysis only = aerobic glycolysis)
Cancer cells up-regulate glucose transporters (GLUT-1)
Hypoxia up-regulate glucose transporters

Glycolysis facilitates cancer cells biosynthesis of macromolecules

Question 20

Genome instability & mutation

Answer 20

Cancer cells increase rates of mutation by:
(the genomes of tumour cells acquire mutations for tumour progression)

• Compromising systems that monitor and detect genomic integrity and force genetically damaged cells into apoptosis and senescence.
• Increased sensitivity to mutagenic agents

(Example of ‘caretaker’ of genome p53 tumour supressor protein)

Question 21

What is the role of caretakers of the genome?

Give an example

Answer 21

p53

caretaker genomes can:

• Detect DNA damage and activate repair machinery
• Directly repair damaged DNA
• inactivate mutagenic molecules before they damage the DNA

Question 22

What is the role of caretakers of the genome?

Give an example

Answer 22

caretakers of the genomes can:

• Detect DNA damage and activate repair machinery
• Directly repair damaged DNA
• inactivate mutagenic molecules before they damage the DNA

Example; p53 and telomerase

p53 in response to DNA damage can elicit cell cycle arrest to allow DNA, repair or apoptosis.

Question 23

Tumour-promoting inflammation

Examples of tumour-promoting inflammatory cells

Answer 23

inflammation supplies bioactive molecules to the tumours microenvironment:
growth factors to sustain proliferative signalling (EGF, VEGF)
induce signals that lead to activation of EMT

E.g. Macrophage, neutrophils

Question 24

Avoiding immune destruction

Answer 24

Highly immunogenic cancer cells can evade immune destruction by disabling components of the immune system.
Cancer cells can secrete T lymphocytes, natural killer cells and recruit inflammatory cells (Treg cells, MDSCs)