Cancer Cell Biology Flashcards
Most cancers arise from…
Epithelial tissues
What are cancers arising in epithelia called?
Carcinomas
What do epithelial cells act together to form?
Glands
What are the cancers of glands called?
Adenocarcinomas
What are cancers of supporting tissues (connective, fat and muscle) called?
Sarcomas
How do you name cancers of the nervous system?
named after originating tissue
What are the cancers of glial tissue called?
Glioblastomas
What are cancers of WBCs called?
Lymphomas and Leukaemias
Hyperplastic tissue (2)
- highly proliferative
- appear normal
Dysplastic tissue (2)
- highly proliferative
- appear abnormal
Metaplastic tissue
original cells are displaced by cells of another type
What is Anaplasia? (3)
- lack of differentiation in cells
- as tumour cells become more abnormal
- so the identity of tissue from which cells have arise cannot be determined
Differentiation is used to grade tumours (3)
Grade 1 - well differentiated
Grade 2 - moderately differentiated
Grade 3 - poorly differentiated
Colorectal cancer originates from… (2)
- Polyps
- Small Adenomas
What are Adenomas?
abnormal outgrowth of the colonic epithelium
Adenomas eventually grow into…
Adenocarcinomas
Colonic epithelium is formed from (1) which is produced by (2)
1) Enterocytes
2) Stem cells
What are the 3 continuous stages that enterocytes go through?
1) Proliferation
2) Upward Migration
3) Apoptosis
When do intestinal stem cells proliferate?
When they receive a WNT signal
What does APC stand for?
Adenomatous Polyposis Coli
What is APC?
A protein that forms a complex to turn off WNT signalling
Mutation of APC (4)
- makes APC non-functional
- hence WNT signalling remains on
- allowing cells to continuously proliferate
- blocking their ability to differentiate and migrate
What releases WNT signals?
Stromal cells
What is WNT?
A ligand (signalling protein) that triggers intestinal stem cells to undergo proliferation
Activation of WNT signalling (5)
(in the presence of wnt)
1) wnt ligands bind to stem cell receptors
2) to inactivate degradation complex which contains APC
3) hence the degradation complex won’t target beta-catenin
4) hence beta-catenin levels remain high
5) beta-catenin binds to TFs to induce cell proliferation
Deactivation of WNT signalling (5)
(in the absence of wnt)
1) degradation complex becomes active
2) it acts as a ligase
3) to phosphorylate and ubiquinate the beta-catenin
4) causing to be shipped to proteasome to be degraded
5) hence beta-catenin can no longer activate gene expression
Name 4 things that contribute to Colorectal cancer
- APC mutation
- FAP
- Loss of TSG
- K-Ras mutation
How does APC mutation contribute to colorectal cancer? (5)
1) beta-catenin levels remain high
2) gene expression remains active
3) stem cell proliferation continues
4) failure to migrate upwards and remain undifferentiated
5) polyp/small adenoma formation
What does FAP stand for?
Familial Adenomatous Polyposis
Features of FAP (3)
- increases risk of colorectal cancer
- due to APC mutation
- hundreds to thousands of polyps develop due to FAP
How does loss of Tumour Suppressor Genes contribute to colorectal cancer? (4)
- loss of p53 and TGF-beta tumour suppressors
- results in failure to arrest cell cycle
- results in failure to induce apoptosis
- hence unrestrained cell proliferation
How does Ras mutation contribute to colorectal cancer? (4)
- further mutations involving K-Ras
- subtype of Ras G-protein
- cells gain advantage to proliferate independently
- hence growth of adenoma
Hallmarks of cancer (6)
1) Sustaining Proliferative Signalling
2) Evading Growth Suppressors
3) Resisting Cell Death
4) Enabling Replicative Immortality
5) Inducing Angiogenesis
6) Activating Invasion and Metastasis
Hallmarks of Cancer:
Sustaining Proliferative Signalling (4)
- receptor overexpression
- hyper-responsive to mitogens
- activate ligand independent mitogenic signalling (caused by mutations)
- develop autocrine signalling
Hallmarks of Cancer:
Evading Growth Suppressors (2)
- TSGs arrest cell cycle or trigger apoptosis
- TSG inactivation
Hallmarks of Cancer:
Resisting Cell Death (4)
Cancer cells:
- activate pro-survival factors (Bcl2)
- inhibit death factors (Bax and Bak)
- block activation of capsases
- resulting in blockade of apoptosis
Hallmarks of Cancer:
Enabling Replicative Immortality (4)
- senescence and apoptosis prevent cells becoming immortal
- telomere shortening induces apoptosis in normal cells
- cancer cells activate telomerase to extend telomeres
- acquiring immortality
Hallmarks of Cancer:
Inducing Angiogenesis (4)
- growth of tumour requires O2 and nutrients
- cancer cells activate pro-angiogenic signalling (VEGF, PDGF) in endothelial cells
- they also suppress the function of angiogenic inhibitors e.g. thrombospondin-1 (TSP-1)
- net result is proliferation of endothelial cells and activation of angiogenesis
Hallmarks of Cancer:
Activating invasion and metastasis (6)
- cancer cells undergo cellular transformation: epithelial-mesenchymal transition (EMT)
- they induce down regulation of cell adhesion molecules (CAMs)
- normally CAMs establish adherens junction
- loss of CAMs = destabilisation of adherens junction
- cancer cells become motile
- resulting in activation of invasion
