TCA cycle nutrient use and invasiveness of ovarian cancer (WP3252)
Bos taurus
Schematic showing the shift in nutrient utilization in TCA cycle with increasing degree of invasiveness. Low-invasive ovarian cancer (OVCA) cells are glucose dependent for their TCA cycle pool. With increasing invasiveness in cancer cells, dominant nutrient which feeds the TCA cycle shifts from glucose to Gln. In high-invasive OVCA cells, Gln dominates the TCA cycle. In low-invasive OVCA cells, glucose activates Jak1, which activates STAT3 by tyrosine phosphorylation, thereby regulating glycolysis in cancer cells. In highinvasive OVCA cells, besides glucose's role in activating STAT3 tyrosine phosphorylation, glutamine activates JAK1 through TCA cycle to further activate STAT3 by tyrosine phosphorylation and thus regulate glycolysis. Further, Gln activates Erk1/2, which subsequently activates STAT3 by serine phosphorylation selectively in high-invasive OVCA cells. The serine phosphorylation of STAT3 enhances oxidative phosphorylation in mitochondria by interaction with mitochondrial complexes I and II, thereby increasing TCA cycle activity in high-invasive OVCA cells.
Authors
Martina Summer-Kutmon , Friederike Ehrhart , and Eric WeitzActivity
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Organisms
Bos taurusCommunities
Annotations
Disease Ontology
cancer reproductive system diseasePathway Ontology
altered citric acid cycle pathway cancer pathwayLabel | Type | Compact URI | Comment |
---|---|---|---|
Lactate | Metabolite | hmdb:HMDB0000190 | |
D-Glutamine | Metabolite | hmdb:HMDB0003423 | |
Pyruvate | Metabolite | hmdb:HMDB0000243 | |
Glucose | Metabolite | hmdb:HMDB0000122 | |
STAT3 | GeneProduct | ensembl:ENSBTAG00000021523 | HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6774 |
MAPK3 | GeneProduct | ensembl:ENSBTAG00000016156 | HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5595 |
JAK1 | GeneProduct | ensembl:ENSBTAG00000003147 | HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3716 |
MAPK1 | GeneProduct | ensembl:ENSBTAG00000010312 | HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5594 |
EGFR | GeneProduct | ensembl:ENSBTAG00000011628 | HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1956 |
References
- Metabolic shifts toward glutamine regulate tumor growth, invasion and bioenergetics in ovarian cancer. Yang L, Moss T, Mangala LS, Marini J, Zhao H, Wahlig S, et al. Mol Syst Biol. 2014 May 5;10(5):728. PubMed Europe PMC Scholia