TCA Cycle Nutrient Utilization and Invasiveness of Ovarian Cancer (Bos taurus)

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1Complex IISuccinate-UbiquinoneLegendComplex INADH-UbiquinoneCancer stageTyrosine phosphorylation pathwayLow-invasive Ovarian CancerLactateTCA CycleGlucoseMAPK3EGFRJAK1D-GlutaminePyruvateMAPK1STAT3Tyr-PGlucoseSTAT3Ser-PGlucoseEGFRJAK1STAT3Tyr-PHigh-invasive Ovarian CancerSerine phosphorylation pathwayMetabolix flux


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.


This pathway was inferred from Homo sapiens pathway WP2868(78079) with a 100.0% conversion rate.

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  1. Yang L, Moss T, Mangala LS, Marini J, Zhao H, Wahlig S, Armaiz-Pena G, Jiang D, Achreja A, Win J, Roopaimoole R, Rodriguez-Aguayo C, Mercado-Uribe I, Lopez-Berestein G, Liu J, Tsukamoto T, Sood AK, Ram PT, Nagrath D; ''Metabolic shifts toward glutamine regulate tumor growth, invasion and bioenergetics in ovarian cancer.''; Mol Syst Biol, 2014 PubMed Europe PMC Scholia


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108105view10:16, 29 November 2019FehrhartOntology Term : 'cancer pathway' added !
105917view11:45, 16 August 2019MaintBotHMDB identifier normalization
89887view13:02, 6 October 2016MkutmonOntology Term : 'altered citric acid cycle pathway' added !
89886view13:01, 6 October 2016MkutmonModified description
80886view15:29, 30 June 2015MkutmonNew pathway

External references


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NameTypeDatabase referenceComment
D-GlutamineMetaboliteHMDB0003423 (HMDB)
EGFRGeneProductENSBTAG00000011628 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1956
GlucoseMetaboliteHMDB0000122 (HMDB)
JAK1GeneProductENSBTAG00000003147 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3716
LactateMetaboliteHMDB0000190 (HMDB)
MAPK1GeneProductENSBTAG00000010312 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5594
MAPK3GeneProductENSBTAG00000016156 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5595
PyruvateMetaboliteHMDB0000243 (HMDB)
STAT3GeneProductENSBTAG00000021523 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6774
TCA CyclePathwayWP78 (WikiPathways)

Annotated Interactions

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