Cancer cell metabolism reprogramming

This class

- Role of oncogenes and tumor suppressors on cell metabolism

- Warburg effect and anabolic pathways
- Glucose and monocarboxylate transporters
 Cell cycle

mitogenic
stimulus PI3K/Akt mTOR Cyclin D/CDK4/6
Ras MAPK
E2F E2F P P
G0 pRB pRB
E2F E2F P P
M G1
E2F E2F
G1 restriction point E2F
E2F
Cyclin B/CDK1
G2
cyclin E

S Cyclin E/CDK2

Cyclin A/CDK2 cyclin A

Oncogenes X Tumor supressor Genes (and their products)
Warburg effect
ATP yield/glucose molecule
Warburg effect
glucose

Preferential metabolism glycolisis Preferential metabolism

in normal cells in tumor cells

pyruvate lactate

H+ H+
H+
H+ Acetyl CoA
APD+Pi ATP
H+
O2+e-+H+ H2O
Tricarboxylic
H+ e- NADH acid cycle
FADH2
Pathways linked to glycolysis ATP
Glucose

ADP hexokinase
glycogen gluconeogenesis Glucose-6P

Fructose-6P

phosphofructokinase
Fructose-1,6P

(x2) Dihydroxyacetone P Glyceraldehyde -3P diacylglycerol

NAD+
1,3- NADH
triacylglycerol
biphosphoglycerate
ADP
ATP
3-phosphoglycerate

Phospho alanine malate

enolpyruvate
ADP
ATP
lactate pyruvate mitochondria – TCA cycle
NAD+ NADH
Pentose Phosphate Pathway
Anabolic pathways linked to glycolysis Glucose
HK Glucose-6P

ATP
fatty acid synthesis,
NADPH
oxidative stress protection

6-phosphoglucone
d-lactone

6-phospho-
gluconate

NADPH pyrimidine
synthesis
Ribulose-5P

5-phosphoribosyl-
xylulose-5P Ribose-5P
1-pyrophosphate

glyceraldehyde
fructose-6P
-3P

glycolysis TCA/oxphos
Serine synthesis/
folate and methionine cycles
Serine synthesis/folate and methionine cycles cellular localization
ONCOGENES X TUMOR SUPRESSORS
ONCOGENES
Hypoxia activated factor

Mitogenic
Stimuli/
nutrients
C-MYC
C-MYC
C-MYC
C-MYC
TUMOR SUPPRESSORS
LBK
PTEN
TUMOR SUPPRESSORS GF

PP2A
GFR
BCR/ABL

PIP3 PDK1
PI3K Akt
PIP2 mTORC2
CYTOPLASM

GSK3 mTORC1
PP2A
SET
protein synthesis
metabolic reprogramming
apoptosis cell survival
ceramide
mediated proliferation
apoptosis
MYTOCHONDRIA BLC-2

Bim
NUCLEUS
Elk1 CIP2A expression
Bad
BLC-2

CIP2A
apoptosis MAPK

PP2A SET
MEK

RAF PP2A
CYTOPLASM SET
Ras-GDP
Ras-GTP PCDH7
BCR/ABL
GFR

GF
TUMOR SUPPRESSORS
TP53
Glucose transporters
GLUT Family
Monocarboxylate transporters