Cell stress Flashcards
List some cancer cell responses to metabolic stress
Carbon uptake and metabolism
Nitrogen uptake and metabolism
Scavenging
Autophagy
What is glucose a source of?
Carbon and energy
________________ deregulation (PI3K / PTEN) leads to
constitutive glucose uptake via ________________
Phosphatidylinositol / RTK
AKT/ GLUT1/HK
What can be mutated for GLUT1 to always be expressed?
PI3K
How do cancer cells use glucose?
For carbon instead of ATP
What do cancer cells produce?
lactate from pyruvate (prefer anaerobic metabolism)
How is glutamine rate limiting?
Only one nitrogen from each glutamine can be used and nucleotides require roughly 1-3 nitrogens
Describe glutamine transport
Passive
By ATP
Antiport (used to import other amino acids into cell)
What is scavenging?
Taking resources from neighbouring cells
Which mutations allow scavenging?
Ras
What is involved in production of new proteins?
eIF2
What inhibits autophagy when there are other nutrients around?
mTOR
Depleting arganine from mesothelioma cells activates gcn2. What does this cause?
Cancer cell apoptosis
Which transcription factor activates VEGF and other genes for angiogenesis?
HIF1
How is HIF1 normally produced, when there’s no stress?
Constantly produced and turned over
What normally inhibits glycolysis?
ATP
In cancer cells, glycolysis is no longer
coupled to oxidative phosphorylation, but
instead to…
biosynthesis.
During cancer cell metabolism, _______________ creates _______________, which is a substrate
for glycosylation.
Hexosamine
N-
acetylglucosamine
During cancer cell metabolism, the ______________ shuttle creates ______________, a major competent of
phospholipids and membranes.
DHAP
glycerol-3-
phosphate
During cancer cell metabolism, ______________ is produced which is precursor for
serine and glycine amino acids
3-phosphoglycerate
Cancer cells express the PMK_ version of pyruvate kinase.
2
Which cancers can glutamine be traced in?
Glioblastoma
cmyc is often overexpressed in cancers. What does this cause?
Increased uptake and use of glutamine
What causes macropinocytosis
Ras/c-Sr
What causes the entosis of living cells?
Ras mutations
How do tumour cells overcome being unable to synthesise fatty acids due to hypoxia?
Uptake of Lysophospholipids (LPS)
Which factors stimulate autophagy
AMPK
HIF
AMPK is overexpressed in…
Glioblastoma multiform.
What senses amino acid starvation?
GCN2
What senses protein misfolding stress?
PERK
What senses haem/iron starvation?
HRI
What senses dsRNA / viral infection?
PKR
What is the The Integrated Stress Response?
Stress sensing pathway
What do stress sensors activate?
eIF2α, which activates the transcription
factor ATF4 (promote survival)
Prolonged or acute stress causes the ISR to activate _____ and cause apoptosis.
CHOP
