Cancer Cell Biology

Question 1

Most cancers arise from…

Answer 1

Epithelial tissues

Question 2

What are cancers arising in epithelia called?

Answer 2

Carcinomas

Question 3

What do epithelial cells act together to form?

Answer 3

Glands

Question 4

What are the cancers of glands called?

Answer 4

Adenocarcinomas

Question 5

What are cancers of supporting tissues (connective, fat and muscle) called?

Answer 5

Sarcomas

Question 6

How do you name cancers of the nervous system?

Answer 6

named after originating tissue

Question 7

What are the cancers of glial tissue called?

Answer 7

Glioblastomas

Question 8

What are cancers of WBCs called?

Answer 8

Lymphomas and Leukaemias

Question 9

Hyperplastic tissue (2)

Answer 9

• highly proliferative
• appear normal

Question 10

Dysplastic tissue (2)

Answer 10

• highly proliferative
• appear abnormal

Question 11

Metaplastic tissue

Answer 11

original cells are displaced by cells of another type

Question 12

What is Anaplasia? (3)

Answer 12

• lack of differentiation in cells
• as tumour cells become more abnormal
• so the identity of tissue from which cells have arise cannot be determined

Question 13

Differentiation is used to grade tumours (3)

Answer 13

Grade 1 - well differentiated
Grade 2 - moderately differentiated
Grade 3 - poorly differentiated

Question 14

Colorectal cancer originates from… (2)

Answer 14

• Polyps
• Small Adenomas

Question 15

What are Adenomas?

Answer 15

abnormal outgrowth of the colonic epithelium

Question 16

Adenomas eventually grow into…

Answer 16

Adenocarcinomas

Question 17

Colonic epithelium is formed from (1) which is produced by (2)

Answer 17

1) Enterocytes
2) Stem cells

Question 18

What are the 3 continuous stages that enterocytes go through?

Answer 18

1) Proliferation
2) Upward Migration
3) Apoptosis

Question 19

When do intestinal stem cells proliferate?

Answer 19

When they receive a WNT signal

Question 20

What does APC stand for?

Answer 20

Adenomatous Polyposis Coli

Question 21

What is APC?

Answer 21

A protein that forms a complex to turn off WNT signalling

Question 22

Mutation of APC (4)

Answer 22

• makes APC non-functional
• hence WNT signalling remains on
• allowing cells to continuously proliferate
• blocking their ability to differentiate and migrate

Question 23

What releases WNT signals?

Answer 23

Stromal cells

Question 24

What is WNT?

Answer 24

A ligand (signalling protein) that triggers intestinal stem cells to undergo proliferation

Question 25

Activation of WNT signalling (5) (in the presence of wnt)

Answer 25

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

Question 26

Deactivation of WNT signalling (5) (in the absence of wnt)

Answer 26

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

Question 27

Name 4 things that contribute to Colorectal cancer

Answer 27

- APC mutation - FAP - Loss of TSG - K-Ras mutation

Question 28

How does APC mutation contribute to colorectal cancer? (5)

Answer 28

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

Question 29

What does FAP stand for?

Answer 29

Familial Adenomatous Polyposis

Question 30

Features of FAP (3)

Answer 30

- increases risk of colorectal cancer - due to APC mutation - hundreds to thousands of polyps develop due to FAP

Question 31

How does loss of Tumour Suppressor Genes contribute to colorectal cancer? (4)

Answer 31

- 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

Question 32

How does Ras mutation contribute to colorectal cancer? (4)

Answer 32

- further mutations involving K-Ras - subtype of Ras G-protein - cells gain advantage to proliferate independently - hence growth of adenoma

Question 33

Hallmarks of cancer (6)

Answer 33

1) Sustaining Proliferative Signalling 2) Evading Growth Suppressors 3) Resisting Cell Death 4) Enabling Replicative Immortality 5) Inducing Angiogenesis 6) Activating Invasion and Metastasis

Question 34

Hallmarks of Cancer: Sustaining Proliferative Signalling (4)

Answer 34

- receptor overexpression - hyper-responsive to mitogens - activate ligand independent mitogenic signalling (caused by mutations) - develop autocrine signalling

Question 35

Hallmarks of Cancer: Evading Growth Suppressors (2)

Answer 35

- TSGs arrest cell cycle or trigger apoptosis - TSG inactivation

Question 36

Hallmarks of Cancer: Resisting Cell Death (4)

Answer 36

Cancer cells: - activate pro-survival factors (Bcl2) - inhibit death factors (Bax and Bak) - block activation of capsases - resulting in blockade of apoptosis

Question 37

Hallmarks of Cancer: Enabling Replicative Immortality (4)

Answer 37

- senescence and apoptosis prevent cells becoming immortal - telomere shortening induces apoptosis in normal cells - cancer cells activate telomerase to extend telomeres - acquiring immortality

Question 38

Hallmarks of Cancer: Inducing Angiogenesis (4)

Answer 38

- 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

Question 39

Hallmarks of Cancer: Activating invasion and metastasis (6)

Answer 39

- 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