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PHAM02 > Wk 9: Hallmarks of cancer > Flashcards

Wk 9: Hallmarks of cancer Flashcards

1
Q

Outline the properties of carcinoma in situ

A
  • Loss of stratification
  • Immature cells
  • Basement membrane intact
  • Cellular dysregulation
  • No longer perform specialist function
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2
Q

What were the original hallmarks of cancer?

A
  • Sustaining proliferative signaling
  • Evading growth suppressors
  • Activating invasion + metastasis
  • Enabling replicative immortality
  • Inducing angiogenesis
  • Resisting cell death
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3
Q

What are the emerging hallmarks of cancer?

A
  • Avoiding immune destruction
  • Tumour promoting inflammation
  • Genome instability + mutation
  • Deregulating cellular energetics
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4
Q

What is cellular growth controlled by?

A
  • Mitogens - stim cell division
  • Growth factors - stim cell growth
  • Survival factors - suppress apoptosis
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5
Q

What are the major components of the cell cycle?

A
  • M phase (mitosis) - cell division
  • Interphase - cell growth + DNA replication
  • Check points
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6
Q

What is the cell cycle?

A
  • Duplicate DNA/C’some
  • Prod 2 identical daughter cells
  • Synthesis: 10-12 hr
  • Mitosis: <1h
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7
Q

Outline the cell cycle

A
  • G1 (interphase)
  • S (interphase)
  • G2 (interphase)
  • M
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8
Q

What is the G1 phase?

A
  • Longest
  • After M phase, cells = half size
  • Cells adapt + grow to normal size
  • Cells repressed + can’t undergo further division
  • Poor nutrition/anti-proliferative signal = enter G1
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9
Q

What is the G0 phase?

A
  • Cell cycle arrest
  • Become specialised
  • Cells active (prod protein, enzyme)
  • Can reenter cell cycle if gene activated
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10
Q

Which cells can’t leave G0 phase?

A

Skeletal + neuronal cells

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11
Q

Which cells are always in G0?

A

Liver cells

  • Tissue don’t express genes encoding CDK + cyclins
  • If damaged, mitogens released, enter G1 + release CDK
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12
Q

What is the S phase?

A

DNA replication

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13
Q

What is the G2 phase?

A
  • Checkpoint (DNA integrity)
  • Enzymes activated
  • Trigger mitosis
  • If faulty, prevent from entering M phase
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14
Q

What occurs in the M phase?

A
  • Prophase
  • Prometaphase
  • Metaphase
  • Anaphase
  • Telophase
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15
Q

Prophase

A

DNA disentangle + condense (sister chromatids)

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16
Q

Prometaphase

A

C’some migrate to equatorial plane in midline

17
Q

Metaphase

A

C’some align along metaphase plate of spindle

18
Q

Anaphase

A

Centromere divide + sister chromatids pulled apart

19
Q

Telophase

A
  • Nuclear membrane reforms
  • C’some uncoil + diffuse
  • Spindle fibre disappears
20
Q

What happens when DNA is damaged?

A
  • Cell cycle arrest + activate DNA damage response
  • Apoptosis
21
Q

What is the cell division cycle 2 (cdc2) protein essential for?

A

Cell cycle progression during:

  • G1 -> S
  • G2 -> M
22
Q

What coordinates the progression of the cell cycle?

A

Cyclins + cyclin dependant kinase (CDK)

23
Q

Outline the classes of cyclins + what they do

A
  • G1/S - activate CDK in late G1
  • S - Activate CDK in S + elevated until mitosis
  • M - activate CDK in G2 -> M
24
Q

What are the 4 major cyclins?

A

D, E, A + B

25
Q

What do cyclins + CDK do?

A
  • Form complex
  • Phosphorylates targets
  • Targets change during cell cyle
26
Q

What are the cell cycle checkpoints?

A
  • G1/S
  • G2/M
  • M/G1
27
Q

G1/S checkpoint

A

Pass:
- Sufficient organelles
- Growth factor activation

Fail:
- TGFβ proliferation inhibitor
- ATP deficiency

28
Q

G2/M checkpoint

A

Pass:
- Completely replicated genome
- Large cell vol

Fail
- DNA damage

29
Q

M/G1 checkpoint

A

Pass:
- Equal distribution of c’some btw daughter cells

Fail:
Chromatid not assembled on spindle

30
Q

Give examples of what causes DNA damage

A
  • Lack of growth factors
  • Excessive mitogenic signalling
  • Chromosomal dysregulation
  • Unreplicated DNA
  • Microtubule spindle defects
31
Q

What are CKIs?

A
  • Bind to cyclin + CDK + distort active site of CDK
  • Insert into ATP binding site + inhibit CDK enzymatic activity
32
Q

Which CKIs inhibit CDK1 + 2 complexes

A
  • p21 (prostate + colon)
  • p27
  • p57 (kidney + skeletal tissue)
33
Q

Give examples of INK4 proteins

A
  • p16: CDK6
  • p15: CDK4
  • p18: CDK 4/6
  • p19: CDK 4/6
34
Q

How does p53 regulate the cell cycle?

A
  • Cell cycle arrest
  • DNA repair
  • Senescence
  • Apoptosis

PHAM02 (35 decks)

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