16 - Hallmarks of Cancer

Question 1

Hallmark 1

Answer 1

Sustaining proliferative signalling

Question 2

Sustaining proliferative signalling

Answer 2

• Normal tissues control the production and release of growth-promoting signals that govern cell growth and division
• Cancer cells deregulate these signals
• Enabling signals are conveyed by growth factors

Question 3

Ways of sustaining proliferative signalling

Answer 3

• Autocrine proliferative signalling
• Elevated levels of receptor proteins
• Signalling to normal cells within associated stroma
• Growth factor independence by constitutive activation of downstream signalling pathways

Question 4

Disruptions of negative-feedback mechanisms that
attenuate proliferative signalling

Answer 4

RAS mutations

Question 5

Hallmark 2

Answer 5

Evading growth suppressors

Question 6

Evading growth suppressors

Answer 6

Evasion of RB and TP53

Question 7

Evasion of RB effects

Answer 7

• Metastasis
• Angiogenesis
• Senescence
• Genome stability
• Cell death
• Differentiation
• g1-s Cell cycle

Question 8

Hallmark 3

Answer 8

Resisting cell death

Question 9

How do tumour cells avoid cell death

Answer 9

• Loss of TP53 tumor suppressor function
• Increasing expression of antiapoptotic regulators (Bcl-2, Bcl-xl)
• Short-circuiting the extrinsic ligand-induced death pathway

Question 10

How do Bcl-2 family regulator proteins (Bcl-2, Bcl-x) inhibit apoptosis

Answer 10

Bind to and suppress Bax and Bak

Question 11

Necrotic pathway

Answer 11

• Cell enlargement
• Loss of membrane integrity
• Leakage of cell contents
• Inflammation (recruitment of immune cells)
• Nuclear degeneration

Question 12

Hallmark 4

Answer 12

Enabling replicative immortality

Question 13

Enabling replicative immortality

Answer 13

Through telomerase

Question 14

Additional functions of telomerase (TERT) in
tumorigenesis

Answer 14

• Amplify signalling by the Wnt pathway
• Enhancement of cell proliferation and/or
• Resistance to apoptosis
• Involvement in DNA-damage repair

Question 15

Hallmark 5

Answer 15

Inducing angiogenesis

Question 16

Angiogenic regulator

Answer 16

Signalling proteins that bind to stimulatory or inhibitory cell-surface receptors

Question 17

Examples of angiogenic regulators

Answer 17

• Vascular endothelial growth factor (VEGF-A)
• Thromboplastin-1 (TSP-1) (inhibitory)

Question 18

Hallmark 6

Answer 18

Activating invasion and metastasis

Question 19

Multistep process of metastasis

Answer 19

• Local invasion
• Intravasation
• Extravasation
• Micro-metastases
• Colonisation

Question 20

E cadherin

Answer 20

• Mediates Contact Inhibition of Proliferation
• Normal cells stop proliferating once they reach confluence upon homophilic E-cadherin binding
• When cells either lose E-cadherin, they continue proliferating, grow on top of each other and lose CIP

Question 21

Loss of E cadherin

Answer 21

Key characteristic of EMT

Question 22

Hallmark 7

Answer 22

Evading immune destruction

Question 23

Reprogramming energy metabolism

Answer 23

• Upregulation of glucose transporters (eg GLUT1) to
  increase glucose transport into the cytoplasm
• Associated with activation of oncogenes
• Hypoxia can also upregulate glucose transporters

Question 24

Aerobic glycolysis / warburg effect

Answer 24

Cancer cells have increased rates of glucose uptake and lactate production, even in the presence of sufficient oxygen and low rate of oxidative phosphorylation

Question 25

Hallmark 8

Answer 25

Reprogramming energy metabolism

Question 26

TGFβ

Answer 26

Significant role in inhibiting T helper cell differentiation and promoting antitumor immunity

Question 27

Enabling characteristics

Answer 27

- Genome instability and mutation - Tumour-promoting inflammation

Question 28

Genomic instability and mutation

Answer 28

- Characteristic of almost all human cancers - The most common is chromosomal instability (CIN)

Question 29

Hereditary cancer genomic instability

Answer 29

The presence of both CIN and non-CIN forms of genomic instability have been linked to mutations in DNA repair genes

Question 30

Sporadic cancer genomic instability

Answer 30

not due to mutations in DNA repair genes or mitotic checkpoint gene

Question 31

Tumour promoting inflammation

Answer 31

- Linked to transformation, proliferation, angiogenesis, and metastasis - Supplying bioactive molecules such as growth factors and survival factors - Immune cells, through the production of inflammatory mediators (e.g. cytokines) contribute to the survival of the tumor in its microenvironment - The aberrant expression and secretion of proinflammatory by the tumor cells result in the recruitment of immune cells, thus creating a mutual crosstalk