1. MYC, Metabolism and Cancer
Molecular genetics lab
Eungyoung Kim

2. Outline Hallmarks of cancer MYC protein MYC function Building a cell
Nutrient sensing
Intermediary metabolism and macromolecular synthesis
Organelle biogenesis
Cell cycle progression
Cancer therapy and Outlook
미국자료-

3. MYC protein
Hallmarks of cancer

4. MYC protein
Hallmarks of cancer

5. MYC MYC protein Hallmarks of cancer - c-Myc, N-Myc, L-Myc
transcription factor that dimerizes with MAX to bind DNA and regulate gene expression
nuclear localization sequence, DNA-binding domain, helix–loop–helix dimerization domain,
and transcriptional regulatory domain underlie this functional ability.

6. MYC protein
Hallmarks of cancer
MYC enhances transcription and translation

7. MYC protein Hallmarks of cancer Growth factor dependent MYC activity
Growth factor independent MYC activity

8. MYC protein
Hallmarks of cancer
MYC regulation in noncancerous and cancerous cells

9. MYC function Hallmarks of cancer 1. Building a cell
Maintenance of cell membrane potentials, homeostasis for redox control and protein synthesis,
are major energy-demanding cellular processes that must be sustained for survival.
in the case of resting memory T cells
1) a major source of energy for homeostasis is a futile cycle of oxidation of de novo–synthesized lipids
2) MYC-mediated proliferating cells use de novo lipogenesis to produce membranes for cell growth
; Glucose and glutamine carbons are imported into cells and converted to citrate for lipogenesis
; resting T cells oxidize the de novo–.synthesized fatty acids for ATP production.
Once stimulated, T cells begin to acquire nutrients, particularly glucose and
glutamine, and convert them to the necessary components for making new DNA
and RNA, new enzymes, new cytoskeleton, new membranes, new organelles,
and new copies of genetic material

10. 2. Nutrient sensing, FOXO, HIF, and MYC
MYC function
Hallmarks of cancer
2. Nutrient sensing, FOXO, HIF, and MYC
lower organisms have developed nutrient-sensing mechanisms that are coordinated with growth.
Nutrient insufficiency causes decreased TORC signaling, resulting in the inhibition of the production of
ribosomes and cell growth through the activation of DOT6 and TOD6
In mammalian cells; With severe starvation or pathologic processes that disrupt tissue perfusion,
cell-autonomous nutrient-sensing mechanisms protect cells through pathways aimed at preserving
adequate ATP pools.
The mTOR, AMP kinase (AMPK), and GCN2 pathways are
key to survival of cells under nutrient deprivation.
Lack of amino acids attenuates mTOR activity through sensing by
the RAG proteins on the lysosomal membrane

11. 2. Nutrient sensing, FOXO, HIF, and MYC
MYC function
Hallmarks of cancer
2. Nutrient sensing, FOXO, HIF, and MYC
Mammalian MYC activity also depends on nutrient status sensed through mTOR via mTOR’s regulation of MYC translation
nutrient sufficiency and growth factor signaling are required for MYC to carry out its transcriptional program
With nutrient starvation, diminished TOR activity attenuates
cell growth through diminished expression of dMyc. This
pathway appears to involve TOR-dependent AKT phosphorylation

12. 2. Nutrient sensing, FOXO, HIF, and MYC
MYC function
Hallmarks of cancer
2. Nutrient sensing, FOXO, HIF, and MYC
With nutrient starvation, diminished TOR activity attenuates
cell growth through diminished expression of dMyc. This
pathway appears to involve TOR-dependent AKT phosphorylation

13. MYC function
Hallmarks of cancer
3. Intermediary metabolism and macromolecular synthesis

14. MYC function
Hallmarks of cancer
4. Organelle biogenesis
Ribosome

15. Mitochondria Other organelles MYC function Hallmarks of cancer
4. Organelle biogenesis
Mitochondria
Other organelles

16. MYC function
Hallmarks of cancer
5. Cell cycle progression

17. MYC function
Hallmarks of cancer
5. Cell cycle progression

18. cancer therapy involved the use of anti-folates LDHA inhibitor
Cancer therapy and Outlook
Hallmarks of cancer
cancer therapy involved the use of anti-folates
LDHA inhibitor
GLS inhibitor
lactate exporter MCT1 inhibitor
NAMPT inhibitor ….
→ combination therapy would be the most promising
metabolic inhibition strategy in the clinic

19. Thank you for your attention
Hallmarks of cancer
Thank you for your attention