Unit 2 - Cancer cell biology

Question 1

How does cancer develop in gradual stages?

Answer 1

-Colorectal cancer : originates from
polyps/small adenomas
* Adenomas are abnormal outgrowth of the colonic epithelium
* Adenomas eventually grow into
adenocarcinomas through a sequence
of mutations

Question 2

How does loss of function mutation of the APC gene lead to the formation of polyps?

Answer 2

• APC acts as a transcription factor >inhibits wnt signalling
  -Loss of function mutation of APC would cause inactivation of APC > continues wnt signalling
  -Intestinal stem cells hyper-proliferate > leading to formation of polyps.

Question 3

What are hallmarks of cancer?

Answer 3

-Traits common to cancer cells…..
-Deviations of normal cell biology which help us understand multi-step process of cancer.

Question 4

What are the 6 main hallmarks of cancer?

Answer 4

1. Sustaining proliferative signalling
2. Evading growth suppressor
3. Resisting cell death
4. Enabling replicative immortality
5. Inducing angiogenesis
6. Activating invasion and metastasis

Question 5

1. Sustaining proliferative signalling

Answer 5

• Mutation of receptor/ signalling protein
  -Leading to ligand independent signalling

Question 6

2. Evading growth suppressor

Answer 6

-Mutation of tumour suppressor gene
-enables cells to avoid cell cycle arrest
e.g. RB/P53

Question 7

3. Resisting cell death

Answer 7

*Upregulation of anti-apoptotic proteins
* And inhibit death factors BAX/BAK
* Block activation of caspases
- Resulting in blockade of apoptosis

Question 8

4. Enabling replicative immortality

Answer 8

• Telomere shortening induces apoptosis in normal cells
• Cancer cells activate telomerase to extend telomeres
• Acquire immortality

Question 9

5. Inducing angiogenesis

Answer 9

• Growth of tumour requires O2 and nutrients - angiogenesis
• Cancer cells activate pro-angiogenic signalling ) in endothelial cells
• They also suppress the function of angiogenic inhibitors
• Net result is proliferation of endothelial cells and activation
  of angiogenesis when they shouldn’t

Question 10

6. Activating invasion and metastasis

Answer 10

• They induce downregulation of cell adhesion molecules (CAMs)
• Normally CAMs establish adherens junctions
• Loss of CAMs = destabilisation of adherens junction
• Cancer cells become motile
• This results in activation of invasiveness

Question 11

How do we stage cancer?

Answer 11

TNM
> T: size of tumour

> N: whether cancer cells have spread to lymph nodes
-N0 no cancer near lymphs
-N1,N2,N3 refer to the location of lymph nodes which contain cancer

> M: Cancer cells have metastasised to other parts of body
-M0 Has not
-M1 cancer has metastasised to another part of body

Question 12

How do we grade cancer?

Answer 12

Differentiation
-Grade 1 : Well differentiated
-Grade 2 : Moderately differentiated
-Grade 3 : Poorly differentiated (more likely to metastasis)
> Low to high grade