HIF DRIVES LIPID DEPOSITION AND
CANCER IN CCRCC VIA REPRESSION
O F FAT T Y A C I D M ETA B O L I S M
B Y: O F U R E A K H I G B E
D AT E : 3 0 A P R I L 2 0 2 0
INTRODUCTION
Clear cell
caused by
lipid and
glycogen
rich deposit
Also known as
renal cell
carcinoma
occurs in both
sporadic and
heritable forms
Different
subtypes of
renal cell
carcinoma:
Clear-cell
INTRODUCTION
Fatty acid (FA) synthesis is
an anabolic process that
responds
to excess citrate in the
cytoplasm.
Metabolism of glucose
under
aerobic conditions
produces pyruvate
Citrate
can also be produced
from metabolism of
glutamine via αketoglutarate in cancer
cells
either through forward flux
through
oxaloacetate, or through
reverse cycle activity of
isocitrate dehydrogenase
and aconitase
Enters the citric acid
cycle in mitochondria by the action
of pyruvate dehydrogenase to
produce acetyl-CoA, and then
citrate-by-citrate synthase.
Produce citrate
FATE OF THE EXCESS CITRATE
exported to the cytosol,
where it is
a substrate for ATP citrate
lyase to produce cytosolic
acetyl-CoA.
carboxylation of
acetyl-CoA by acetylCoA carboxylase
to form malonyl-CoA
malonyl-CoA
to fatty acid
ROLE OF FATTY ACID
To serve as
substrates for
membrane
synthesis,
Energy stores
Production of
signaling
molecules.
Abnormal cancer
metabolism leads
to excessive
storage in the
form of lipids.
GOAL OF THE RESEARCH
To determine the molecular mechanisms driving lipid
deposition in ccRCC.
MATERIAL/METHOD
Mouse
tumor
assays
Fatty acid
uptake
assay
Materials
and
Methods
Chromatin
Immunopreci
pitation(ChIP)
Cell
culture
and
reagents
Oil red O
staining
Real time
PCR
Western
blots
RESULT
Lipid droplet formation requires glucose, but not glutamine.
Together, the
observations suggest
lipid droplet formation in
ccRCC cells is highly
dependent on glucose
rather than glutamine
RESULTS
Lipid droplet formation is dependent on HIF.
OVERALL CONCLUSION
Metabolic adaptation in clear cell renal cell carcinoma resulting in activation of
lipid storage pathways is a necessary step in the development of malignancy.
Metabolic changes in ccRCC include shifts to anaerobic metabolism through the
HIF-dependent activation of many genes in the glycolytic pathway, reductive
carboxylation of glutamine derived α-ketoglutarate as a carbon source in place
of pyruvate in the citric acid cycle.
FOLLOW UP EXPERIMENT
Would slowing down or reducing the amount of glucose produced in ccRCC
patients help in reducing lipid deposition?
Follow up Experiment:
 I would cultivate cells from renal cancer patients with lipid deposits and monitor
how the rate of glucose production affects the lipid deposition
THINGS I LEARNED FROM MY
INTERVIEW:
I interviewed Ms
Ann Cooke
Ms Ann Cooke
was diagnosed
with breast
cancer a day
before her
nineteenth
anniversary
breast cancer
changes a
woman both
physically and
emotionally
Cancer does
not just affect
the body
physically
it is very important
for patients to build
a personal
connection with their
surgeon and team.
REFERENCES
Du, Weinan, et al. “HIF Drives Lipid Deposition and Cancer in CcRCC via
Repression of Fatty Acid Metabolism.” Nature News, Nature Publishing
Group, 24 Nov. 2017, www.nature.com/articles/s41467-017-01965-8.