Molecular Pathology of Cancer Flashcards

1
Q

How does HPV cause cancer?

A

Produces ubiquitin protein E63, which ubiquitinises p53

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2
Q

What are the 6 original hallmarks of cancer?

A
Proliferative signalling 
Replicative immortality
Evading growth suppressors 
Metastasis
Avoiding apoptosis 
Angiogenesis
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3
Q

How do cancer cells sustain proliferation?

A

Autocrine EGF secretion
Paracrine secretion of IGF to stimulate EGF secretion
Increase EGF receptor expression
Loss of inhibitors of proliferation, e.g. TGF-beta

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4
Q

How do cancer cells evade growth suppression?

A

Overcome tumour suppressors, e.g. p53, Rb
Loss of proliferation inhibitors, e.g. TGF-beta
Overcome cell-cell contact proliferation inhibition

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5
Q

How do cancer cells resist cell death?

A

Loss of p53
Loss of pro-apoptosis regulatos, Bax, Bad, Bim, Puma
Gain of anti-apoptotic regulators, e.g. BCL2, BCL-XL
Overcoming signals from ligand-activated death receptors, Fas

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6
Q

How does IGF effect cancer progression?

A

Increase IGF by stromal cells, causes EGF secretion

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7
Q

How do cancer cells promote angiogenesis?

A

Increased VGEF and FGF
Reduced anti-angiogenic factors, e.g. thrombospondin-1
Hypoxia

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8
Q

How do cancer cells enable replicative immortality?

A

Increased telomerase

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9
Q

How do cancer cells activate invasion and metastasis?

A

Epithelial to mesenchyme transition via:
downregulation of E-cadherinIs
Increase matrix metalloproteases (MMPs), Rac

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10
Q

What are the four emerging hallmarks of cancer?

A

Switch to glycolysis, immune system evasion, mutation, tumour-promoting inflammation.

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11
Q

Which mutation is responsible for 50% of lung adenocarcinomas?

A

Epidermal growth factor receptor having constitutive activity.

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12
Q

How is p53 regulated?

A

ATM (DNA breaks) and ATR (stress) increase p53.

Ubiquitin ligases MDM2 and MDM4 dimerise in the absence of stress to ubiquitinise p53

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13
Q

How are epigenetics modified in cancer cells?

A

Increased methylation and acetylation to reduce transcription of certain genes.

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