TCA Cycle Nutrient Utilization and Invasiveness of Ovarian Cancer (Homo sapiens)

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Complex INADH-UbiquinoneComplex IISuccinate-UbiquinoneTyrosine phosphorylation pathwayLow-invasive Ovarian CancerLegendCancer stageGlucoseD-GlutamineERK1JAK1LactateTCA CycleSTAT3ERK2EGFRPyruvateTyr-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 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.

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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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112051view17:09, 17 September 2020KhanspersOntology Term : 'ovarian cancer' added !
112050view17:06, 17 September 2020Khanspersupdated phospho sites and added references
108102view10:15, 29 November 2019FehrhartOntology Term : 'cancer pathway' added !
106479view19:43, 3 September 2019KhanspersModified description
106190view12:08, 16 August 2019MaintBotHMDB identifier normalization
105431view04:31, 8 August 2019KhanspersModified description
105408view15:55, 7 August 2019DeSlSmall layout changes to make textLabels more readable.
105391view17:51, 6 August 2019KhanspersModified description
105390view17:51, 6 August 2019KhanspersModified description
105389view17:50, 6 August 2019KhanspersModified description
105388view17:50, 6 August 2019KhanspersModified description
105387view17:49, 6 August 2019KhanspersModified description
90260view23:06, 27 October 2016AlexanderPicoChanged Stat3 to default node color
89885view13:01, 6 October 2016MkutmonModified description
78079view23:52, 30 November 2014Khanspersfixed unconnected interactions
77985view18:05, 4 November 2014KhanspersAdded lit ref and fixed arrow
77984view18:04, 4 November 2014KhanspersOntology Term : 'reproductive system disease' added !
77983view18:03, 4 November 2014KhanspersModified description
77956view19:38, 30 October 2014KhanspersOntology Term : 'altered citric acid cycle pathway' added !
77955view19:34, 30 October 2014KhanspersOntology Term : 'cancer' added !
77954view19:34, 30 October 2014KhanspersModified description
77917view20:00, 29 October 2014KhanspersModified title
77916view19:59, 29 October 2014KhanspersNew pathway

External references


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NameTypeDatabase referenceComment
D-GlutamineMetaboliteHMDB03423 (HMDB)
EGFRGeneProduct1956 (Entrez Gene)
ERK1GeneProduct5595 (Entrez Gene)
ERK2GeneProduct5594 (Entrez Gene)
GlucoseMetaboliteHMDB00122 (HMDB)
JAK1GeneProduct3716 (Entrez Gene)
LactateMetaboliteHMDB00190 (HMDB)
PyruvateMetaboliteHMDB00243 (HMDB)
STAT3GeneProduct6774 (Entrez Gene)
TCA CyclePathwayWP78 (WikiPathways)

Annotated Interactions

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