TCA cycle nutrient use and invasiveness of ovarian cancer (Homo sapiens)
From WikiPathways
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. Protein phosphorylation sites were added based on information from PhosphoSitePlus (R), www.phosphosite.org.
Proteins on this pathway have targeted assays available via the CPTAC Assay Portal
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Ontology Terms
Bibliography
- Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V, Skrzypek E; ''PhosphoSitePlus, 2014: mutations, PTMs and recalibrations.''; Nucleic Acids Res, 2015 PubMed Europe PMC Scholia
- 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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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
D-Glutamine | Metabolite | HMDB0003423 (HMDB) | |
EGFR | GeneProduct | 1956 (Entrez Gene) | |
ERK1 | GeneProduct | 5595 (Entrez Gene) | |
ERK2 | GeneProduct | 5594 (Entrez Gene) | |
Glucose | Metabolite | HMDB0000122 (HMDB) | |
JAK1 | GeneProduct | 3716 (Entrez Gene) | |
Lactate | Metabolite | HMDB0000190 (HMDB) | |
Pyruvate | Metabolite | HMDB0000243 (HMDB) | |
STAT3 | GeneProduct | 6774 (Entrez Gene) | |
TCA cycle | Pathway | WP78 (WikiPathways) |
Annotated Interactions
No annotated interactions