Cell stress

Question 1

List some cancer cell responses to metabolic stress

Answer 1

Carbon uptake and metabolism

Nitrogen uptake and metabolism

Scavenging

Autophagy

Question 2

What is glucose a source of?

Answer 2

Carbon and energy

Question 3

________________ deregulation (PI3K / PTEN) leads to
constitutive glucose uptake via ________________

Answer 3

Phosphatidylinositol / RTK

AKT/ GLUT1/HK

Question 4

What can be mutated for GLUT1 to always be expressed?

Answer 4

PI3K

Question 5

How do cancer cells use glucose?

Answer 5

For carbon instead of ATP

Question 6

What do cancer cells produce?

Answer 6

lactate from pyruvate (prefer anaerobic metabolism)

Question 7

How is glutamine rate limiting?

Answer 7

Only one nitrogen from each glutamine can be used and nucleotides require roughly 1-3 nitrogens

Question 8

Describe glutamine transport

Answer 8

Passive
By ATP
Antiport (used to import other amino acids into cell)

Question 9

What is scavenging?

Answer 9

Taking resources from neighbouring cells

Question 10

Which mutations allow scavenging?

Answer 10

Ras

Question 11

What is involved in production of new proteins?

Answer 11

eIF2

Question 12

What inhibits autophagy when there are other nutrients around?

Answer 12

mTOR

Question 13

Depleting arganine from mesothelioma cells activates gcn2. What does this cause?

Answer 13

Cancer cell apoptosis

Question 14

Which transcription factor activates VEGF and other genes for angiogenesis?

Answer 14

HIF1

Question 15

How is HIF1 normally produced, when there’s no stress?

Answer 15

Constantly produced and turned over

Question 16

What normally inhibits glycolysis?

Answer 16

ATP

Question 17

In cancer cells, glycolysis is no longer
coupled to oxidative phosphorylation, but
instead to…

Answer 17

biosynthesis.

Question 18

During cancer cell metabolism, _______________ creates _______________, which is a substrate
for glycosylation.

Answer 18

Hexosamine

N-
acetylglucosamine

Question 19

During cancer cell metabolism, the ______________ shuttle creates ______________, a major competent of
phospholipids and membranes.

Answer 19

DHAP

glycerol-3-
phosphate

Question 20

During cancer cell metabolism, ______________ is produced which is precursor for
serine and glycine amino acids

Answer 20

3-phosphoglycerate

Question 21

Cancer cells express the PMK_ version of pyruvate kinase.

Answer 21

2

Question 22

Which cancers can glutamine be traced in?

Answer 22

Glioblastoma

Question 23

cmyc is often overexpressed in cancers. What does this cause?

Answer 23

Increased uptake and use of glutamine

Question 24

What causes macropinocytosis

Answer 24

Ras/c-Sr

Question 25

What causes the entosis of living cells?

Answer 25

Ras mutations

Question 26

How do tumour cells overcome being unable to synthesise fatty acids due to hypoxia?

Answer 26

Uptake of Lysophospholipids (LPS)

Question 27

Which factors stimulate autophagy

Answer 27

AMPK HIF

Question 28

AMPK is overexpressed in…

Answer 28

Glioblastoma multiform.

Question 29

What senses amino acid starvation?

Answer 29

GCN2

Question 30

What senses protein misfolding stress?

Answer 30

PERK

Question 31

What senses haem/iron starvation?

Answer 31

HRI

Question 32

What senses dsRNA / viral infection?

Answer 32

PKR

Question 33

What is the The Integrated Stress Response?

Answer 33

Stress sensing pathway

Question 34

What do stress sensors activate?

Answer 34

eIF2α, which activates the transcription factor ATF4 (promote survival)

Question 35

Prolonged or acute stress causes the ISR to activate _____ and cause apoptosis.

Answer 35

CHOP