Molecular Pathology of Cancer Flashcards
How does HPV cause cancer?
Produces ubiquitin protein E63, which ubiquitinises p53
What are the 6 original hallmarks of cancer?
Proliferative signalling Replicative immortality Evading growth suppressors Metastasis Avoiding apoptosis Angiogenesis
How do cancer cells sustain proliferation?
Autocrine EGF secretion
Paracrine secretion of IGF to stimulate EGF secretion
Increase EGF receptor expression
Loss of inhibitors of proliferation, e.g. TGF-beta
How do cancer cells evade growth suppression?
Overcome tumour suppressors, e.g. p53, Rb
Loss of proliferation inhibitors, e.g. TGF-beta
Overcome cell-cell contact proliferation inhibition
How do cancer cells resist cell death?
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
How does IGF effect cancer progression?
Increase IGF by stromal cells, causes EGF secretion
How do cancer cells promote angiogenesis?
Increased VGEF and FGF
Reduced anti-angiogenic factors, e.g. thrombospondin-1
Hypoxia
How do cancer cells enable replicative immortality?
Increased telomerase
How do cancer cells activate invasion and metastasis?
Epithelial to mesenchyme transition via:
downregulation of E-cadherinIs
Increase matrix metalloproteases (MMPs), Rac
What are the four emerging hallmarks of cancer?
Switch to glycolysis, immune system evasion, mutation, tumour-promoting inflammation.
Which mutation is responsible for 50% of lung adenocarcinomas?
Epidermal growth factor receptor having constitutive activity.
How is p53 regulated?
ATM (DNA breaks) and ATR (stress) increase p53.
Ubiquitin ligases MDM2 and MDM4 dimerise in the absence of stress to ubiquitinise p53
How are epigenetics modified in cancer cells?
Increased methylation and acetylation to reduce transcription of certain genes.
