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

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Tyrosine phosphorylation pathway Complex I NADH-Ubiquinone Complex II Succinate-Ubiquinone Low-invasive Ovarian Cancer Cancer stage Legend Tyr-P STAT3 Lactate JAK1 D-Glutamine Pyruvate Glucose EGFR TCA Cycle ERK1 ERK2 Glucose Ser-P STAT3 Glucose EGFR JAK1 Tyr-P STAT3 High-invasive Ovarian Cancer Serine phosphorylation pathway Metabolix flux Name: TCA Cycle Nutrient Utilization and Invasiveness of Ovarian Cancer Organism: Homo sapiens


Description

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.

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Ontology Terms

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Bibliography

  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

History

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RevisionActionTimeUserComment
98142view 17:02, 19 November 2018AlexanderPicoModified title
98141view 17:01, 19 November 2018AlexanderPico
90260view 16:06, 27 October 2016AlexanderPicoChanged Stat3 to default node color
89885view 06:01, 6 October 2016MkutmonModified description
78079view 16:52, 30 November 2014Khanspersfixed unconnected interactions
77985view 11:05, 4 November 2014KhanspersAdded lit ref and fixed arrow
77984view 11:04, 4 November 2014KhanspersOntology Term : 'reproductive system disease' added !
77983view 11:03, 4 November 2014KhanspersModified description
77956view 12:38, 30 October 2014KhanspersOntology Term : 'altered citric acid cycle pathway' added !
77955view 12:34, 30 October 2014KhanspersOntology Term : 'cancer' added !
77954view 12:34, 30 October 2014KhanspersModified description
77917view 13:00, 29 October 2014KhanspersModified title
77916view 12:59, 29 October 2014KhanspersNew pathway

External references

DataNodes

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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

<cite>No annotated interactions</cite>