Signal Transduction and Cancer

Question 1

What is signal transduction?

Answer 1

the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events which ultimately results in a cellular response

Question 2

What are some general rules of signal transduction?

Answer 2

• pathway activation is rapid and transient (short lasting)
• persistent activation of a pathway may lead to uncontrolled cell proliferation (cancer)
• pathways are multi component = intracellular signalling molecules can compromise of proteins, small molecules or lipids
• target proteins are post-transitionally modified which results in conformational changes

Question 3

What are post-translational modifications?

Answer 3

• generally enzymatic modification of proteins following protein biosynthesis
• occurs in the endoplasmic reticulum and the Golgi apparatus
• approx 523 kinases
• other types of post translational modifications are:
  1. Acetylation
  2. Methylation
  3. Lipid conjugation
  4. Ubiquitination
• all have deactivating enzymes

Question 4

What is signal specificity?

Answer 4

• different ligands bind to their own specific receptors
• the same ligand can induce a different response in different cell types as the same ligand can bind different receptors and can utilise different intracellular signalling molecules to transmit the signal
• different signals differentially lead to the activation of different transcription factors
• different cell types express dissimilar transcription factors, therefore the same signal results in expression of different genes in different cell types

Question 5

What are examples of intracellular receptors?

Answer 5

• steroids
• retinoids
• vitamin D

Question 6

What are examples of transmembrane receptors?

Answer 6

• ion channels
• G protein-coupled
• tyrosine kinases

Question 7

List some regulatory elements with their transcription factors and triggers

Answer 7

1. GGGANNNTCC, NF-kB, immune stress
2. TGACGTCA, CREB, cyclic AMP
3. GGTCANNNTGACC, oestrogen receptor, oestrogen
4. GAAANNGAAACTG, ISGF3, interferon

Question 8

What are downstream effects of G coupled protein receptors

Answer 8

• glycogen breakdown
• ion channel regulation
• transcriptional activation
• Ca2+ Influx
• cytoskeletal rearrangements

Question 9

What is the result of overexpression of EGFR and ERBB2

Answer 9

• EGFR = responsible for over 50% of carcinomas
• ERBB2 = responsible for 30% breast cancer

Question 10

What is the result of active procto-oncogenes RAS and RAF?

Answer 10

RAS:
- 20-30% human tumours
- 90% pancreatic adenocarcinoma
- 50% colon/thyroid adenocarcinoma
- 30% lung adenocarcinoma
RAF:
- 7% human tumours
- 70% melanomas
- 30% thyroid cancer
- 15% colon cancer

Question 11

How is cancer a defect in cell signaling?

Answer 11

• The wiring of intracellular signalling is extremely specific and is regulated by transient changes in affinity of key components
• cancer can disrupt correct associations of cellular components through mutations which will short circuit intracellular signaling