L17: Reprogramming Energy Metabolism In Cancer

Question 1

What are the 6 hallmarks of cancer

Answer 1

Sustaining proliferative signalling 
Evading growth suppressors
Resisting cell death 
Activating invasion and metastasis 
Inducing angiogenesis
Enabling replicative immortality

Question 2

What are the 4 other hallmarks added to the 6 hallmarks

Answer 2

Deregulating cellular energetic
Avoiding immune destruction
Genome instability and mutations
Tumour promoting inflammation

Question 3

What is required to permit the cancer hallmarks

Answer 3

Metabolic transformation

Question 4

What are the 3 nutrients for a cell metabolism

Answer 4

Lipids
Carbs
Proteins

Question 5

What are lipids important in

Answer 5

Cell membrane and energy

Question 6

What is carbs used for

Answer 6

Produce DNA, proteins, cell membrane and energy

Question 7

What are proteins used

Answer 7

Brocken into amino acids to produce DNA and energy

Question 8

In normal cells how is energy obtained in aerobic conditions

Answer 8

1) glycolysis: glucose is converted to pyruvate

2) TCA cycle: Pyruvate is metabolised

Question 9

How many energy i.e ATP is obtained from a normal cell in arerobic condition

Answer 9

36 ATP

Question 10

How does a normal cell obtain energy in anaerobic conditions

Answer 10

Glycolysis occurs only

Question 11

In cancer how is energy metabolised

Answer 11

Using glycolysis only even in aerobic condition

Question 12

At what rate does glycosis in cancer cells run

Answer 12

Fast

Question 13

What is the Warburg effect in cancer

Answer 13

when cancer cells switch to glycolysis which occurs in aerobic conditions and produces the breakdown product of lactate as a result

Question 14

What also the Warburg effect in cancer to take place

Answer 14

Activation of oncogenes and/or loss of tumour suppressor genes

Question 15

What is the role of PTEN

Answer 15

To inhibit the PI3K pathway and stop cell survival and proliferation

Question 16

To make PI3K pathway occur in cancer what can happen to PTEN

Answer 16

Mutates to remove its effect

Question 17

If PTEN is removed what protein is activated that removes inhibitory apoptosis protein from BAD so apoptosis is inhibited

Answer 17

AKT

Question 18

What other role does active AKT have

Answer 18

• Increases glucose uptake by increasing GLUT-4 on the cell surface
• Increase the rate of glycolysis by activating the enzyme PFK

Question 19

What are the other way in activating akt

Answer 19

Mutation of RAS

Question 20

What is the normal role of P53 in terms of glycolysis and oxidative phosphorylation

Answer 20

P53 decreases glycolysis and increases oxidative phosphorylation = opposes effect of the Warburg effect

Question 21

What does P53 help maintain

Answer 21

The mitochondria

Question 22

How does P53 maintain oxidative phosphorylation

Answer 22

By transcription and activation of SC02 which is a regulator of cytochrome c oxidase complex in the electron transport chain

Question 23

What can happen to P53 in tumours

Answer 23

Deficienct i.e knocked out

Mutated

Question 24

What happens if P53 is knocked out

Answer 24

TCA is not functional and glycolysis occurs= Warburg effect

Question 25

What happens if P53 is mutated instead

Answer 25

It will retain its ability to up regulate enzymes involved in: 1) detox oxidative stress 2) dna/rna synthesis 3) oxidative atp generation 4) increased glucose consumption

Question 26

What does normal P53 do to the uptake of glucose

Answer 26

Inhibit the uptake of glucose by inhibiting transcription of glut 1 and glut 4 and glut 3

Question 27

What is c-MHC

Answer 27

A gene

Question 28

What does c-myc regulate

Answer 28

Lipogenesis Ribosome genesis Glycolysis Glutamineloysis

Question 29

If c-myc is amplified in cancer what does it become

Answer 29

An oncogenes

Question 30

What does amplification of c-myc mainly lead to

Answer 30

Glutamineolysis

Question 31

What is glutamineolysis

Answer 31

Glutamine metabolism

Question 32

What does glutamine metabolism allow in the cancer cell

Answer 32

Produce many bio synthetic intermediates to help drive cell proliferation

Question 33

How does K-RAS mutation change metabolism of cancer cells

Answer 33

- Increase uptake of proteins- used to generate new proteins e.g DNA and RNA - permanently activate AKT which increases glycolysis

Question 34

In familiar cancer syndrome what happens

Answer 34

Enzymes involved in the TCA cycle can become mutation

Question 35

What does mutations of enzymes in the TCA cycle lead to

Answer 35

HIF activation

Question 36

What does HIF activate

Answer 36

Angiogenesis Proliferation Cell survival Increased glycolysis