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 Weitz

Activity

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Organisms

Bos taurus

Communities

Annotations

Disease Ontology

cancer reproductive system disease

Pathway Ontology

altered citric acid cycle pathway cancer pathway

Participants

Label 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

  1. 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