CANCER TRAITS 3

Question 1

What is the aerobic cell metabolism

Answer 1

• glucose is turned into pyruvate (via glycolysis) in cytosol, then turned into CO2 via oxidative phosphorylation in the mitochondria
• uses -36 mol ATP/mol glucose

Question 2

what is the anaerobic cell metabolism

Answer 2

• glucose to pyruvate via glycolysis then pyruvate is turned into lactate via fermentation
• uses 2 mol ATP/mol glucose

Question 3

What is cancer cell metabolism

Answer 3

when cancer cells adjust energy metabolism to fuel cell growth and division

Question 4

what is cancer cell metabolism called

Answer 4

aerobic glycolysis or the warburg effect
- even in oxygen presence, energy metabolism is limited to glycolysis and lactate production

Question 5

How do cancer cells reprogramme their metabolism

Answer 5

• Glucose transporters
• activation oncogenes (e.g. Ras, Myc)
• mutation of tumour suppressors
  -Reliance on glycolysis is more noticeable under hypoxia–> upregulates GLUTs & other enzymes
• This reprogramming seems counterintuitive; cancer cells must compensate for lower ATP production
• Glycolisis intermediates used for biosynthesis of macromolecules (e.g. amino acids) & organelles required for assembling new cells

Question 6

so what do cancerous cells do instead of producing more energy?

Answer 6

they produce metabolites that can be reused (recycling process) - therefore creating the building blocks of producing new cells and they get that by changing their metabolism by lactate fermentation

Question 7

How are mutations rare in normal cells?

Answer 7

DNA sequences remain intact & mutations are rare due to:
Genome maintenance systems & repair enzymes; detect & fix DNA
DNA monitoring; monitor genomic integrity & force damaged cells into senescence or apoptosis
Multiple mutations are unlikely to occur within human life span

Question 8

How does cancer cells increase mutation traits?

Answer 8

by compromising:
Components of genomic maintenance system–> increasing sensitivity to mutagenic agents
Surveillance systems

yet cancers are frequent: genomes of tumour cells acquire increased mutability

Question 9

What are genome caretakers

Answer 9

Defects of DNA maintenance system (caretakers of the genome) can affects genes involved in:
Detecting DNA damage & activating repair machinery
Directly repairing damaged DNA
Inactivating mutagenic molecules before DNA damage occurs
Assuring correct chromosomal segregation during mitosis

Question 10

what are example of ‘caretakers’

Answer 10

-P53 tumour suppressor: in response to DNA damage–> cell cycle arrest to allow DNA repair or apoptosis

-Telomerase: loss of telomeric DNA–> genome instability & chromosomal abnormalities

• Apoptosis: apoptotic body DNA can be incorporated into neighbouring cells–> genetic diversity of tumour cell types

Question 11

What genomic instability

Answer 11

Genomic instability is intrinsic to human cancer cells
Large number of genome maintenance & repair defects
Defects in genome maintenance & repair are advantageous for tumour progression
Accelerate rate at which precancer cells accumulate favourable genotypes

Question 12

How do tumours promote inflammation?

Answer 12

infiltrated with innate & adaptive immune cells causing inflammation

Question 13

what are the genes involved in that the defects of DNA maintenance system has affected?

Answer 13

Detecting DNA damage & activating repair machinery
Directly repairing damaged DNA
Inactivating mutagenic molecules before DNA damage occurs
Assuring correct chromosomal segregation during mitosis

Question 14

what is paradoxically?

Answer 14

tumour associated inflammation enhance tumorigenesis & cancer progression

Question 15

What are the tumour promoting inflammatory cells?

Answer 15

Macrophages
Mast cells
Neutrophils
T & B lymphocytes

Question 16

Inflammation supplies bioactive molecules to tumours, what are the examples?

Answer 16

1. Growth factors (EGF)–> sustain proliferative signalling
2. Survival factors–> limit cells death
3. Pro-angiogenic factors (cytokines)
4. Extracellular, matrix-modifying enzymes (MMPs)–> facilitate angiogenesis, invasion & metastasis
5. Inductive signals–> activate EMT

Question 17

What is immune surveillance?

Answer 17

Immune system (innate & adaptive cells) monitors cells & tissues
Recognises & eliminates developing tumours

Question 18

How do cancer cells evade immune surveillance?

Answer 18

1. Disrupting CTLs (cytotoxic T lymphocytes) & NK (natural killer cells) through secretion of immunosuppressive factors (TGF-beta)
2. Recruiting immunosuppressive inflammatory cells (Tregs, MDSCs)
   3.Interfering with antigen presentation by downregulating parts of antigen processing machinery or antigen expression–> CTLs no longer recognise tumour antigens
   4.Tolerance & immune deviation:
   Don’t express co-stimulatory molecules–> anergy or tolerance in T cells
   Change T cell subtypes
   Express inhibitory molecules like programmed death ligand (PD-L1)

Question 18

what are tregs?

Answer 18

regulatory T cells

Question 19

How do solid tumours do?

Answer 19

or limit immunological killing–> avoid eradication

Question 20

what are MDSCs?

Answer 20

myeloid derived suppressor cells

Question 21

what do progenitor cells do?

Answer 21

differentiate into specialist cell types (terminal differentiation) or continue to replicate (self renewal)

Question 22

How can cancer cells change differentiation state?

Answer 22

Dedifferentiated back to progenitor states
Remain partially differentiated
Change differentiation pathway (transdifferentiation)

Question 23

what are epigenetic changes?

Answer 23

genome changes without alterations in DNA sequence

changes in gene activity and expression produced by DNA methylation and histone modification

epigenetic reprogramming in cancer can affect tumour heterogeneity and microenvironement

Question 24

what is senescence

Answer 24

Changes in cell morphology & metabolism
Activation of senescence-associated secretory phenotype (SASP)–> release of bioactive proteins (cytokines, proteases)

Question 25

What do senescent cancer cells do?

Answer 25

Stimulate tumour growth by:
- Releasing proteins involved in proliferation, apoptosis evasion, angiogenesis, invasion & metastasis, suppression of tumour immunity
- Escaping non-proliferative state & resume proliferation–> viable oncogenic cells

Question 25

What are the polymorphic microbiomes?

Answer 25

Polymorphic variability in microbiomes (bacteria, fungi) between individuals in a population impacts on cancer phenotypes
Can have protective or damaging effects on cancer development, progression & response to therapy