Mol Basis of Cancer (2)

Question 1

6 steps of invasion-metastasis cascade

Answer 1

1- Breaking down basal membrane
2- EMT and Intravasation
3- Anoikis resistance
4- Extravasation
5- Colonisation and MET
6- Dormancy-Proliferation

Question 2

Matrix metalloproteinases play role in …

Answer 2

Invasion
Cleavage of ECM & cell adhesion molecules

Question 3

2 types of Matrix metalloproteinases (MMPs)

Answer 3

1. Transmembrane type MT-MMPs
2. Secreted MMPs

Question 4

2 types of Matrix metalloproteinases (MMPs)

Answer 4

1. Transmembrane type MT-MMPs
2. Secreted MMPs

Question 5

Transmembrane type MT-MMPs (2 functions)

Answer 5

• cleavage by furin during secretion
• accumulation in invadopodia (actin-rich membrane protrusions, which possess the ECM degrading activity)

Question 6

Secreted MMPs (2 functions)

Answer 6

• Extracellular cleavage by other MMPs and plasmin
• Binding to ECM

Question 7

stromal cells can also express ____ to help with invasion

Answer 7

MMPs

Question 8

EMT? (step 2)

Answer 8

Epithelial-mesenchymal transition

EPITHELIAL CELLS LOSE E-CADHERIN AND OTHER EPITHELIAL MARKERS AND ACQUIRE EXPRESSION OF MESENCHYMAL MARKERS RESULTING IN ENHANCED CELL MOTILITY AND INVASIVENESS.

Question 9

5 steps of EMT and intravasation (step 2)

Answer 9

1-Cadherin switch
2-Mucin downregulation
3-Loss of epithelial cell polarity
4-Increased matrix metallo-protease expression
5- Increased mesenchymal markers (such as vimentin)

Question 10

CTCs

Answer 10

Circulating tumour cells
grow in the circulation as clusters & interact with immune cells

Question 11

anoikis resistance

Answer 11

Resistance to detachment-induced cell death

cells that have anoikis resistance and retain mesenchymal status survive in circulation

Question 12

what precedes extravasation

Answer 12

rolling and arrest (tumour cell ligand binds receptor on endothelial cell)

Question 13

ALTERNATIVE EXTRAVASATION PATHWAY

Answer 13

Role of platelets - Trapping (of cancer cell)
(common in liver where vessels are very tiny)

Question 14

MET (step 5-6)

Answer 14

Mesenchymal-epithelial transition

(mesenchymal cancer cells after extravasation, either remain dormant or undergo MET to form secondary tumours)

cancer dissemates
colonises
rapid expansion

Question 15

macrometastasis result in

Answer 15

disease relapse

Question 16

seed and soil hypothesis

Answer 16

“seeds from plants can be carried in all directions but they can only live and grow if they fall on congenial soil”

in cancer: cancer metastasises and colonises similar tissues
e.g. breast ectoderm (similar to skin) -> goes to bone marrow
e.g. Ectoderm makes nerves -> goes to brain

Question 17

Proposed mechanism of MET

Answer 17

Activation of micro RNAs to inhibit EMT TFs such as ZEB1, ZEB2 or TWIST.

Question 18

TGFβ signalling may be key in inducing ____?

Answer 18

EMT-MET cycles